Number Of IgA-secreting Cells Research Articles

Probiotics for prevention of acute respiratory infections in children: therapeutic potential.

Acute respiratory viral infections represent a group of clinically, pathomorphologically similar acute inflammatory respiratory diseases that manifest by fever, a runny nose, sneezing, cough, sore throat, a general feeling of ill health of varying severity. Activation of latent, persistent infections of viral and/or bacterial origin may occur in recurrent respiratory infections. Decreased production of local immunity contributes greatly to the development of viral and bacterial infections, persistence of pathogenic micro-organisms. Intestinal microflora can directly or indirectly affect the human respiratory tract through increased production of cytokines, short-chain fatty acids. In recent years, there has been a scientific interest in the therapeutic potential of probiotics for the prevention of acute respiratory viral infections. Earlier studies have shown a positive effect of probiotics on the respiratory tract with a view to prevent and reduce the incidence and severity of respiratory infectious diseases by expending the number of IgA secreting cells in the bronchial mucosa. Studies showed that the use of probiotics can reduce the incidence of acute respiratory infections, duration of fever, cough, and the need for antibacterial agents in children. Peptidoglycans and muramyl peptides that are constituents of the bacterial cell wall have antiviral activity. Probiotics can also inhibit virus attachment through a process of competing for the specific receptors. The regeneration of the mucous membrane is enhanced by the ability of mucin to prevent the virus from attaching to epithelial cells and suppress virus replication. The antiviral effect of probiotics may be caused by the ability to produce antimicrobial peptides, dehydrogenases and NOs. Probiotics can modulate the functions of epithelial and dendritic cells, CD4 +, CD8 + T lymphocytes, NK cells, stimulate the synthesis of secretory immunoglobulins, helping to neutralize the virus.

Oral administration of Bacillus subtilis promotes homing of CD3+ T cells and IgA-secreting cells to the respiratory tract in piglets

Oral probiotics are used to induce immune responses in the intestines to protect against infection. However, oral probiotics may also affect immune responses in other mucosal tissues such as in the respiratory tract. To examine this possibility, we explored the potential of immunocytes to home to the respiratory system after oral administration of Bacillus subtilis. The results showed that B. subtilis could promote intestinal development and not cause pathological changes in the respiratory tract. Following the oral administration with B. subtilis, the number of IgA-secreting cells and CD3+ T cells not only significantly increased in the intestinal tracts but also in respiratory tracts (P < 0.01). Moreover, the levels of secretory IgA were significantly higher in the trachea, lungs, ileum, and jejunum after oral B. subtilis administration than in the control groups (P < 0.05). The mRNA expression of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, B cell activating factor, and IgA-inducing protein increased following B. subtilis administration (P < 0.01) in the trachea, lungs, ileum, and jejunum. These data suggest that B. subtilis administration regulates the immune response not only in the intestine but also in the respiratory tract of piglets. Our work highlights a potentially new strategy for promoting respiratory mucosal immunity and may contribute to the design of vaccines with B. subtilis as a mucosal adjuvant.

Murine γδ T Cells Render B Cells Refractory to Commitment of IgA Isotype Switching.

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ−/−) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ−/− mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ−/− mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ−/− mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ−/− mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.

Adding crude glycerin to nursery pig diet: Effect on nutrient digestibility, metabolic status, intestinal morphology and intestinal cytokine expression

The objective of this study was to determine the effect of crude glycerin (Gly) added to nursery pig diet on nutrient digestibility, the digestive and metabolic status, intestinal morphology and intestinal cytokine expression. A total of 18 male piglets (weaned at 23 days) were used. There were three dietary treatments that differed in the inclusion level of Gly (0, 9 and 18%). On day 14 of the experiment, the animals were weighed and plasma samples were collected before slaughtering. In addition urine, digesta content and intestinal tissues were sampled post mortem. No differences were observed among the tested diets as regards the coefficients of apparent ileal digestibility of DM and CP. The concentration of lactic acid decreased linearly (P<0.05) in the jejunum and ileum segments as the level of Gly increased, although the concentrations of volatile fatty acids in the cecum and colon were not affected. The plasma concentrations of glucose, fructosamine and IGF-1 were not affected. However, urinary glycerol concentrations increased (P<0.01) with increasing levels of Gly. In general, there were no differences in villus height, crypt depth, villus/crypt ratio or number of lymphocytes in the intestinal segments between the different treatments. Nevertheless, the control treatment produced a higher level of goblet cells in the ileum than either of the Gly treatments (P<0.01), while in the jejunum, the number of IgA-secreting cells in the 9% Gly group was higher (P<0.01) than in the control group. There were no differences among the experimental treatments concerning the gene expression of IL-10, IL-12 p40 and TNF-α. Gene expressions of TGF-β, IL-12 p35, IFN-γ and IFN-α were remained unaffected or increased, depending on the intestinal segment and level of Gly addition. In conclusion, the inclusion of Gly at 9 and 18% to the nursery pig diet did not affect nutrient digestibility or plasma metabolites but increased the levels of urinary glycerol, suggesting that metabolic pathways of glycerol utilization became saturated when high levels of Gly are used. In addition, the intestinal cell structure and intestinal cytokine expression might be affected when Gly is included in the feed.

Importance of the host specificity in the selection of probiotic bacteria

The gastrointestinal tract is a complex and dynamic ecosystem. Commensal microorganisms (C), which proliferate in the intestine from birth, are crucial for gut homeostasis while non commensal (NC) microorganisms are transient and enter the organism from the environment and foods. We studied comparatively the influence of oral administration of C and NC Lactobacillus fermentum and Lactobacilus acidophilus on the gut-associated lymphoid tissue (GALT) of conventional mice. To determine the importance of the selection of probiotic host-specificity bacteria with immunomodulating capacity, we examined the interaction with the gut by transmission electron microscopy and FITC-labelled bacteria. We compared the immunomodulation capacities of C and NC strains by studying the number of IgA secreting cells and cytokine profile. No differences were found in the number of IgA+ cells; however, the pattern of cytokine response to C and NC bacteria was different. With regard to proinflammatory cytokine (IFNgamma and TNFalpha), we found that TNFalpha was mainly produced by NC bacteria, while C bacteria were able to elicit mainly IFNgamma. The regulatory cytokines (IL-10 and IL-4) were induced with different patterns for both C and NC strains. No differences in the pathway of internalization to the gut between C and NC were found. In summary, we determined that C and NC bacteria interact with the intestine in the same way; both C and NC bacteria were able to reinforce the surveillance of the gut mucosal immune system. The cytokine profile showed that C bacteria would be involved in the regulation of intestinal homeostasis rather than in the immune activation as the NC bacteria.

Influence of whey-based fruit juice containing Lactobacillus rhamnosus on intestinal well-being and humoral immune response in healthy adults

The ability of probiotics to balance intestinal microbes and to modulate gut immune system has been reported for several probiotic strains. In the present study, Lactobacillus rhamnosus strain VTT E-97800 (E800) or L. rhamnosus Lc705 (the latter in combination with Propionibacterium freudenreichii ssp. shermanii JS) were separately administered to healthy adult volunteers ( n = 11 in both study groups) in a whey-based fruit juice. Survival of the potentially probiotic L. rhamnosus strains in the GI-tract and their effect on intestinal well-being and peripheral immune parameters were assessed. Both L. rhamnosus strains were recovered in high numbers in faecal samples during the consumption period and with few exceptions they were not detected after the 2 weeks follow-up period. Consumption of the juice supplemented with either of the L. rhamnosus strains did not have significant effect on faecal consistency or defecation frequency. No changes were observed in the immunological parameters (number or immunoglobulin A-, G- and M-secreting cells, expression of Fc α-receptor or complement receptors 1 and 3), except for a slight decrease in the number of IgA secreting cells during ingestion of the juice supplemented with L. rhamnosus Lc705 and P. freudenreichii ssp. shermanii JS. The results indicate that L. rhamnosus strains E800 and Lc705 had good survival ability in the GI-tract when administered in a whey-based fruit juice matrix. No adverse effects on intestinal function or on studied immunological parameters were observed during consumption of the whey based juice drink supplemented with the potential probiotic strains.

Inflammatory Immune Response

Lactic acid bacteria (LAB) are the most commonly used microorganisms in probiotic products and it is known that these LAB enhanced the immune response and increase resistance to neoplasia and infections. In previous studies using an experimental model of BALB/c mice it was demonstrated that a cyclical diet of yoghurt given to animals previously injected with the carcinogen 1,2 dimethylhydrazine (DMH) inhibited the development of colorectal carcinoma. The animals showed an inflammatory response prior to the development of the tumour, which was diminished with the yoghurt feeding. We examined the immunoregulatory and antiinflammatory mechanisms involved in the inhibition of tumour growth by yoghurt and compared with the mechanisms of a non-steroidal antiinflammatory drug (Indomethacin). Five experimental groups (BALB/c mice) were used in this study: 1) DMH group, injected with 1,2 dimethylhydrazine weekly for 10 weeks. 2) DMH-yoghurt group, yoghurt was supplemented 10 days followed by inoculation with DMH. After tumour induction yoghurt was given every 10 days for six months. 3) Only yoghurt given during six months following the same schedule (yoghurt control. 4) DMH-indomethacin group. After tumour induction, animals were treated with indomethacin, injected cyclically. 5) Non-treatment control group fed with a conventional balanced diet. We studied IgA secreting cells and CD4+ and CD8+ T cells in the large intestine of mice fed long term with yoghurt and others treated with indomethacin. TNFα, INFγ cytokines, Bcl2 protein and iNOS enzyme production was also measured We observed an increase in the number of IgA-secreting cells but not in the CD4+ and CD8+ cells in the mice fed long term with yoghurt. Indomethacin treated mice showed high values of all these cellular populations. Mice injected with indomethacin did not show increased levels of the proinflammatory cytokine TNFα and INFγ. These cytokines were increased in DMH and DMH plus yoghurt groups. iNOS enzyme determinations were increased in DMH and DMH plus indomethacin group. These results coincided with the inflammatory response observed in the histological findings. Bcl-2 protein was increased in mice fed long term with yoghurt. We suggest that the immune mechanisms by which yoghurt operates would be different to those induced with the antiinflammatory drug indomethacin. Yoghurt activated the production of cytokines that could exert a regulation of the immune response by apoptosis induced by TNFα. We conclude that yoghurt down modulate the immune response and exert its antitumour activity by its antiinflammatory activity, a mechanism that is different with that of the antiinflammatory indomethacin.

Immunomodulating Effects of Peptidic Fractions Issued from Milk Fermented with Lactobacillus helveticus

The effect of peptides released during the fermentation of milk on the humoral immune system and on fibrosarcoma growth was studied. Lactobacillus helveticus was able to release peptidic compounds during milk fermentation due to its high proteolytic activity, as was shown by the degree of proteolysis and size-exclusion HPLC elution profiles. Three fractions of these compounds were separated and fed to mice during different periods (2, 5, and 7 d). The humoral immune response was assessed by following the number of IgA-secreting cells, and the antitumor activity was monitored by studying the regression of subcutaneously implanted fibrosarcomas. Feeding during 2 and 7 d with the medium-sized fraction (Fraction II) significantly increased the IgA-producing cells in the intestines, whereas feeding with the large compound fraction (Fraction I) during 5 d and the small compound fraction (Fraction III) during all three feeding periods provided similar increases. A double dose of Fraction II showed the highest IgA-producing cell count. The increase by Fraction III was shown to be caused by the presence of L-Tryptophan. Fraction II significantly decreased the size of fibrosarcoma when previously fed during 7 d, and feeding with Fraction I during 5 d decreased significantly its size after 35 d of growth. Although the mechanisms by which lactic acid bacteria enhance the immune system are not clear, this study clearly shows that bioactive compounds released in fermented milks contribute to the immunoenhancing and antitumor properties of these products. The release of bioactive peptides by lactic acid bacteria can have important implications on the modulation of the cellular immune response.

Optimal Effect of Lactobacillus delbruecki subsp. bulgaricus, Among Other Lactobacilli Species, on the Number of IgA and Mast Cells Associated with the Mucosa in Immunosuppressed Mice

In previous papers we demonstrated the influence of the oral administration of different lactic acid bacteria on the systemic immune response and the protective effect against an infection with Candida albicans in a corticoid immunosuppressed experimental model in mice. The gastrointestinal and respiratory tracts are the most common sites of entry of the infectious agents at the mucosal surfaces. The IgA secreting cells and mastocytes play an important role in host defence against pathogens. The aim of this study was to determine whether or not some lactobacilli strains have influence on the number of IgA and mast cells associated with the gut and bronchus mucosa, in mice immunosuppressed by corticoid therapy. Groups of animals were immunosuppressed by corticoid oral administration (50 mg kg-1). They were split into four experimental groups: immunosuppressed control mice and the immunosuppressed test groups, which were given L. casei, L. delbruecki subsp. bulgaricus or L. acidophilus at a concentration of 1 X 109 cells/day/mouse, on days 8 and 9 post-corticoid. We demonstrated that the lactobacilli strains assayed were able to increase the number of IgA secreting cells and mast cells associated with both gut and bronchus mucosa, the effect being more remarkable for L. delbruecki subsp. bulgaricus. The enhancement of the IgA secreting cells and mast cells, in an immunosuppressed host induced by lactobacilli administration specially by L. delbruecki subsp. bulgaricus, suggest the potential of its use as adjuvant therapy to protect mucosal surfaces.

Bifidobacterium bifidum exhibits a lipopolysaccharide-like mitogenic activity for murine B lymphocytes.

To determine the role of bifidobacteria in the systemic and mucosal antibody response, we examined the direct modulatory effect of bifidobacteria on the synthesis of antibodies by murine spleen B cells. Whole spleen B cells were cultured with Bifidobacterium bifidum or Clostridium perfringens (Welch's bacilli, negative control), and antibody synthesis was measured by ELISA and enzyme-linked immunospot assay. The B. bifidum, but not C. perfringens, substantially increased total secretion of major immunoglobulin (Ig) isotypes and the number of IgA-secreting cells. In addition, B. bifidum increased proliferation of spleen cells by threefold, and C. perfringens had little to diminishing effect on the cells. These results indicate that B. bifidum increased Ig synthesis through its mitogenic influence on B cells. Further, B. bifidum induced spleen B cells to be reactive to transforming growth factor-beta 1 and interleukin-5 and resulted in increased surface IgA expression (approximately threefold) and total IgA production (> 20-fold) but not increased production of IgM and IgG2a isotypes. Together, these studies indicate that B. bifidum can act as a lipopolysaccharide-like polyclonal activator for B cells. Furthermore, that bifidobacteria enable B cells to respond to transforming growth factor-beta 1 and interleukin-5 for the IgA production has important implications for the primary defense against pathogens in the gastrointestinal tract.

Effect of yogurt feeding on the small and large intestine associated lymphoid cells in mice.

The effect of giving yogurt supplements to BALB/c mice on the various gut-associated lymphoid cells was studied. Animals were fed for 2, 5, 7 and 10 consecutive days. The different lymphoid cell types were identified and counted by haematoxylin-eosin staining of histological slices. The numbers of cells secreting IgA, IgG and IgM and the numbers of T lymphocytes were determined by direct immunofluorescence. The degree of activation of the intestinal macrophages in the small intestine was assessed by measuring the beta-glucuronidase (EC 3.2.1.31) released into the intestinal fluid, and also by a histochemical method. Throughout the feeding period, there were no histological alterations in the gut, but there was marked cell infiltration, mainly of plasma cells and lymphocytes. The number of macrophages on the small intestine increased significantly after feeding for 2 d, while the beta-glucuronidase activity was only slightly higher that of the controls. After a 7 d feeding period, the number of IgA secreting cells increased, while the values for cells secreting IgM and IgG and for T lymphocytes remained similar to those of the controls. The effect of giving yogurt on lymphoid cells associated with the large intestine was mainly on the numbers of IgA secreting B cells and T lymphocytes, with a marked increase during the whole feeding period in the latter type of cell. Since giving yogurt mainly enhanced the IgA secreting B cells in both small and large intestines, this increase would strengthen the host's defence mechanisms in the intestinal mucosa. Although the number of macrophages was increased, there was no enhancement in their activity, which might have harmed the host by producing an inflammatory response.

A prospective study of humoral immune responses to cow milk antigens in the first year of life.

Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.

Antibody-producing cells in peripheral blood and tonsils after oral treatment of children with bacterial ribosomes

The efficacy of ribosomal preparations as mucosal immunostimulants was examined in the peripheral blood and tonsils of 14 children, before and after 28 days of oral treatment with D-53, a preparation of ribosomes from Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes. Tonsils from 10 untreated children were used as controls. Immunofluorescence and ELISAspot were performed to analyse variations in the numbers of immunoglobulin-containing and immunoglobulin-secreting B-cells. Both isotypic and antigenic specificities of these two types of cells were investigated. Significant differences were observed after treatment in the peripheral blood as well as between tonsils from treated and untreated children. In the peripheral blood a significant increase in immunoglobulin-secreting cells directed against antigenic specificities of D-53 was the major change. In tonsils, higher numbers of specific immunoglobulin-containing and secreting cells, and higher numbers of IgA-secreting cells were induced in treated children. These data support the efficacy of D-53 as an oral immunostimulant.

COW MILK ANTIGENS IN INFANT DIET SIGNIFICANTLY INFLUENCE THE DEVELOPING IMMUNE SYSTEM

The concept of oral tolerance is based on work in experimental animals, but data demonstrating its hypothesized existence in humans is scarce We enrolled 25 healthy term newborns with nonatopie heredity to a prospective study, during; which scheduled visits took place at 3, 6, and 11 mo of age. Diet was determined at each visit Gut humoral immune response was approximated with ELISPOT assay of circulating antibody secreting cells, and serum 1gM, IgA and IgG antibodies to cow milk antigens were measured At 3 mo of age, despite low levels of serum IgA antibodies, cells secreting specific IgA to cow milk antigens were detected in the formula fed group, but not in breastfed infants The number of these cells decreased between the 6 and 11 mo visits, remaining at a measurable lesel. The total number of IgA secreting cells increased with age (p=0.001) The milk in the infant's diet inlluenced this development the age related increase was significantly greater in the formula fed group (p=0.04). The results indicate that diet significantly affects the developing immune system. Further, healthy infants, unlike those with cow milk allergy, are able to produce a local antigen specific immune response to dietary antigens. This could be crucial in attaining clinical tolerance of such antigens

Accelerated expression of secreted alpha-chain gene in anaphylactoid purpura.

The mechanisms of the elevation of serum IgA levels in anaphylactoid purpura were investigated. Serum IgA levels were significantly elevated within 2 weeks (5 to 14 days for all 12 patients) after onset in patients with anaphylactoid purpura. Serum IgM and IgG were not elevated. Although the percentages of surface IgA-bearing cells were not increased in the patients, the numbers of IgA-secreting cells within 2 weeks after onset in the patients with anaphylactoid purpura were significantly higher than those of controls. In northern blot analysis on lymphocytes, the secreted alpha (alpha s)-chain gene was well expressed compared with the membrane-bound alpha (alpha m)-chain gene, within 2 weeks after the onset of anaphylactoid purpura. Therefore, stimulation by a certain agent or a certain immune response may accelerate expression of the alpha s-chain gene in anaphylactoid purpura.

Immunoglobulin producing cells in bone marrow and blood of patients with multiple sclerosis and controls.

Multiple sclerosis (MS) is characterised by intrathecal synthesis of IgG, less frequently of IgA and IgM. Local production of antibodies to myelin basic protein (MBP) and other myelin components has also been reported, and autoimmune pathogenesis has been postulated. Whether MS is accompanied by a systemic B cell response is less clear. To elucidate this question, we examined bone marrow and peripheral blood from patients with MS and controls for cells secreting IgG, IgA and IgM, as well as anti-MBP antibodies of these three isotypes. Patients with MS without any signs of concurrent infections had higher numbers of IgG + IgA + IgM secreting cells both in bone marrow and peripheral blood compared with healthy controls. The same abnormalities were observed in patients with other inflammatory neurological diseases (OIND). When analysing individual isotypes, patients with MS and OIND had higher numbers of IgA secreting cells both in bone marrow and blood compared with healthy controls. Only one of 13 MS patients examined had anti-MBP antibody secreting cells in bone marrow and blood. The systemic B cell response registered in MS is also present in other inflammatory neurological diseases and its specificity and possible role in the pathogenesis of MS remains unknown.

Transforming growth factor beta 1 increases IgA isotype switching at the clonal level.

Transforming growth factor beta 1 (TGF beta 1) has important effects on expression of the IgA isotype. TGF beta 1 alone, or in combination with IL-5 or IL-2 increases IgA secretion by populations of LPS-activated surface IgA negative (sIgA-) spleen B cells, while concurrently decreasing IgM and IgG secretion. The present study demonstrates the activity of TGF beta 1 as an IgA isotype switch factor at the clonal level. Stimulation of LPS-activated sIgA- spleen B cell populations with TGF beta 1, or a combination of TGF beta 1 and IL-2, resulted in a significant increase in total numbers of IgA secreting cells, and this increase ultimately was paralleled by an increase in total IgA secretion. Using limiting dilution analysis, TGF beta 1 was shown to increase the frequency of IgA secreting B cell clones, by approximately 20-fold. This was not accompanied by increased numbers of IgA secreting cells/clone. In contrast, IL-2 does not have activity as an IgA switch factor, but does increase IgA production by B cells already committed to secrete that isotype. Cell cycle inhibitors such as thymidine and hydroxyurea also selectively increased numbers of IgA secreting cells and total IgA secretion among populations of LPS-activated sIgA- spleen B cells. This suggests the IgA enhancing activity of TGF beta 1 may, in part, be related to its ability to inhibit cell growth.

Autologous Mixed Lymphocyte Reaction and T-Cell Suppressor Activity in Patients with Henoch-Schönlein Purpura and IgA Nephropathy

To assess the existence of persistent abnormalities in the cellular mechanisms regulating the immunoglobulin (Ig) synthesis in Henoch-Schönlein purpura (HSP) and IgA nephropathy, we studied through a hemolytic plaque assay (PFC) the response to the autologous mixed lymphocyte reaction (AMLR) and the T-cell suppressor activity in 24 patients with IgA nephropathy, in 20 individuals with inactive HSP (IHSP) and in 18 normal controls. In the group with IgA nephropathy there was a significant increase in the number of IgA-secreting cells after AMLR (p less than 0.01), and 9 of the 15 patients tested had an impaired generation of T-cell suppressor activity. No such abnormalities were found in individuals with IHSP. These findings support the existence of persistent defect in the mechanisms regulating the Ig synthesis, limited only to the patients with IgA nephropathy.

Normal human intestinal B lymphocytes. Increased activation compared with peripheral blood.

The state of activation of normal human intestinal mononuclear cells obtained from transplant donors was studied. Compared with PBMC, freshly isolated intestinal mononuclear cells expressed significantly more cell surface activation antigens on both B and T lymphocytes. Intestinal mononuclear cells contained significant numbers of immunoglobulin secreting cells immediately after cell separation. This population included CD5-positive B cells that secreted predominantly IgA. Cells from the large bowel consistently revealed higher numbers of IgA secreting cells than cells from the small bowel. Thus, intestinal B cells are markedly activated in vivo compared with PBMC and this increased activation correlates with increased spontaneous antibody secretion. B cells from the large intestine are more highly activated and secrete more antibody than do cells from the small intestine. The intestinal lamina propria lymphoid compartment exhibits a heightened state of activation that may be important for its distinct role in mucosal defense.

Interleukin 5 is a differentiation factor for IgA B cells.

Interleukin 5 (IL5) stimulates murine B cells to IgA production in vitro. The present study examined the B cell target of IL5 activity, and asked whether IL5 acts as an isotype switch factor, a growth factor, or a differentiation factor on B cells that produce the IgA isotype. Lipopolysaccharide-activated surface IgM-positive, surface IgA-positive or surface IgA-negative B cell populations from spleen or Peyer's patches were stimulated with IL5, after which the expression of cell surface IgA, IgA secretion, and numbers of IgA-secreting cells were determined. IL5 increased the IgA response by acting on B cells that are already committed to IgA expression. Thus, with regard to the IgA response, IL5 acts as a differentiation factor, rather than a growth or IgA isotype switch factor.