Immunoglobulins In Response Research Articles

ImmunoProtective Role of Medicinal Herbs as Phytotherapeutic Drugs in Ayurveda – A Prospective Approach for Defending COVID19

The present review article elucidates the phytotherapeutic applications of various herbal medicines and plant products in Ayurveda for curing diseases and promoting health through boosting our immunity. This could serve as an immune protective tool in defending the antagonistic effects of the present Covid-19 pandemic. The plants with various phyto-immunomodulatory constituents could be a perspective approach for combating the antagonistic effects of COVID-19 and possibly developing immunity to fight against the upcoming health issues related to it. A list of potential herbs with their phyto protective constituents is described in this review. Our immunity plays a significant role in defending the adverse impacts of foreign antigens and synthesizes some protective biomolecules called immunoglobulins in response to that. Various naturally occurring bioactive compounds are isolated from medicinal herbs. In this regard, Ayurvedic therapy employs the ability of various immunomodulatory phytoconstituents derived from medicinal herbs to cure the ailments. In the current era of medicinal research, scientific investigations on the role of immunomodulatory phytoconstituents in the modulation of immunity have gained utmost importance. In light of this, several medicinal plants and their Ayurvedic Rasayana with immunomodulatory activity have been reported. Some of these plants are, Cinnamomum zeylanicum Garcin ex Blume, Glycyrrhiza glabra L., Adhatoda vasica L., among various immunomodulatory phytoconstituents Cinnamaldehyde, Eugenol, Glycyrrhizin, isoliquiritin, vasicine, Adhatodic acid, have notable phytoimmunomodulatory effects for effective management of COVID-19.

Lsh/HELLS is required for B lymphocyte development and immunoglobulin class switch recombination

Mutation of HELLS (Helicase, Lymphoid-Specific)/Lsh in human DNA causes a severe immunodeficiency syndrome, but the nature of the defect remains unknown. We assessed here the role of Lsh in hematopoiesis using conditional Lsh knockout mice with expression of Mx1 or Vav Cre-recombinase. Bone marrow transplantation studies revealed that Lsh depletion in hematopoietic stem cells severely reduced B cell numbers and impaired B cell development in a hematopoietic cell-autonomous manner. Lsh-deficient mice without bone marrow transplantation exhibited lower Ig levels in vivo compared to controls despite normal peripheral B cell numbers. Purified B lymphocytes proliferated normally but produced less immunoglobulins in response to in vitro stimulation, indicating a reduced capacity to undergo class switch recombination (CSR). Analysis of germline transcripts, examination of double-stranded breaks using biotin-labeling DNA break assay, and End-seq analysis indicated that the initiation of the recombination process was unscathed. In contrast, digestion-circularization PCR analysis and high-throughput sequencing analyses of CSR junctions and a chromosomal break repair assay indicated an impaired ability of the canonical end-joining pathway in Lsh-deficient B cells. Our data suggest a hematopoietic cell-intrinsic role of Lsh in B cell development and in CSR providing a potential target for immunodeficiency therapy.

TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes

B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of Tcells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized. Here, we show that the transient receptor potential melastatin 5 channel (TRPM5), which is one of the CAMs, negatively modulates calcium signaling, thereby regulating LPS-induced proliferative and inflammatory responses by B cells. LPS-stimulated B cells of Trpm5-deficient mice exhibit an increased cytosolic calcium concentration, leading to enhanced proliferation and the production of the inflammatory cytokines interleukin-6 and CXCL10. Furthermore, Trpm5-deficient mice show an exacerbation of endotoxic shock with high mortality. Our findings demonstrate the importance of TRPM5-dependent regulatory mechanisms in LPS-induced calcium signaling of splenic B cells.

The Effects of Checkpoint Blockade and a CD40 Agonist on Tindependent and T-dependent Antibody Responses in Mice: Implications for Optimization of Vaccination Strategies in Patients Receiving Immunotherapies

Background: Patients with cancer often do not receive vaccines to preventable infectious diseases such as influenza and pneumococcal pneumonia because of a lack of knowledge about the optimal timing of vaccination relative to their underlying disease or their current cancer treatments. Cancer immunotherapies, which rely on the ability to promote immune responsiveness to tumors, are a promising therapeutic modality, but their impact on vaccination is largely unexplored.Methods: We used a pre-clinical mouse model to evaluate the antibody response to a T-dependent (TD) or a Tindependent (TI) antigen immunization with concomitant administration of either checkpoint inhibitors such as antibodies to CTLA-4 or PD-L1 or an antibody to CD40 that has adjuvant properties.Results: We found that checkpoint blockade with anti-CTLA-4 or anti-PD-L1 antibodies provided reduction in IgM, IgG, and most IgG subclasses when immunized with either TI or TD antigens. On the other hand, a CD40 agonist antibody provoked modest reductions in all immunoglobulins in response to TD antigen but provided marked increases in most immunoglobulins and IgG subclasses in response to TI antigen.Conclusions: These data suggest that the timing of vaccinations relative to immunotherapies might be an important factor in determining the efficacy of vaccination. If these findings are shown to extend to humans, the antibody response to vaccination might be attenuated and patients might be at increased risk for infection. This pilot study provides potential mechanistic insights into an important consideration in patients receiving immunotherapies.

Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics.

The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune repertoires in groups of rats after immunization with purified antigens. Proteomics and NGS data on the repertoire are in qualitative agreement, but did show quantitative differences that may relate to differences between the biological niches that were sampled for these approaches. Both methods contributed complementary information in the characterization of the immune repertoire. It was found that the immune repertoires resulting from each antigen had many similarities that allowed samples to cluster together, and that mutated immunoglobulin peptides were shared among animals with a response to the same antigen significantly more than for different antigens. However, the number of shared sequences decreased in a log-linear fashion relative to the number of animals that share them, which may affect future applications. A phylogenetic analysis on the NGS reads showed that reads from different individuals immunized with the same antigen populated distinct branches of the phylogram, an indication that the repertoire had converged. Also, similar mutation patterns were found in branches of the phylogenetic tree that were associated with antigen-specific immunoglobulins through proteomics data. Thus, data from different analysis methods and different experimental platforms show that the immunoglobulin repertoires of immunized animals have overlapping and converging features. With additional research, this may enable interesting applications in biotechnology and clinical diagnostics.

Ageing adversely affects the migration and function of marginal zone B cells.

SummaryMarginal zone (MZ) B cells are positioned within the spleen to capture blood‐borne antigen and immune complexes and deliver them to follicular dendritic cells in the B‐cell follicles. We show that within the spleens of aged mice antigen capture by MZ B cells, and their ability to shuttle between the follicle and MZ, were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine‐1‐phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B‐cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T‐cell‐independent (TI) antibody‐responses to microbial polysaccharide antigen. In aged mice the ability to produce immunoglobulins in response to the TI type 1 antigen TNP‐LPS was impaired. These ageing‐related changes to the MZ and MZ B cells have implications for the clearance of blood‐borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI antigen, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing‐related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.

Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss). Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.

Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.

Effect of maternal dietary manipulation and in ovo injection of nutrients on the hatchability indices, post-hatch growth, feed consumption, feed conversion ratio and immunocompetence traits of turkey poults

ABSTRACTTwo hundred turkey breeder hens and 24 viable toms of 30-35 weeks (wk) old of small white variety were distributed into 2 treatment groups having 4 replicates First four replicates were offered diet A [National Research Council. 1994. Nutrient requirements of poultry. 8th ed. Washington, DC: National Academy Press] and other four replicates were maintained on a higher plane of nutrition – diet B for 8 wk. Five hundred and fortyeight fertile eggs on 21st embryonic day were in ovo injected with nutrients (essential amino acids - INA; linolenic acid, linoleic acid, retinol and DL-alpha-tocopherol-INFV; INA + INFV-INAFV, sham control – S and un-injected control – C). INAFV poults had significantly (P < .01) higher body weight compared to other treatment groups till 8 wk of age. Total immunoglobulins in response to 1% sheep red blood cells were significantly higher (P < .01) in the INA group compared to the C group. Cell-mediated immune response was significantly higher (P < .01) in the diet B group compared to diet A group. Thus, INAFV treatment may be carried out for better posthatch growth and breeders may be maintained on higher plane of nutrition along with INA treatment to elicit better post-hatch immunity.

Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: Tailoring better vaccination strategies

Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients.

Mice deficient in Complement Receptor 1 produce normal to enhanced quantities of antigen specific immunoglobulin in response to naïve immune challenge (172.14)

Abstract Complement receptors (Cr)1 and 2 have been established to have important roles in control of complement activation in the immune microenvironment and B cell responses. Previous work investigating the effects of these receptors in vivo has relied on a double knockout mouse line in which each of these receptors was deleted. However, two drawbacks of this mouse must be acknowledged: 1) that both receptors are deleted and roles of each must be inferred, and 2) that the essential B cell signaling protein CD19 is expressed at a significantly higher level than WT cells. We have created a Cr1 deficient line of mice (expressing Cr2) by homologous gene targeting that expresses normal levels of Cr2 gene products on B cells. This animal has normal ratios of bone marrow, B2 cell, and B1 B cell populations. Cr2 negative marrow B cells express the same amount of surface CD19 as WT but mature Cr2-expressing B cells express less. These Cr2-only mice generate normal to slightly enhanced antibody titers to T-dependent and T-independent (both 1 and 2 antigens.) In conclusion Cr1 is not critical for development and maintenance of B cell populations nor for the generation of antibodies to naïve antigens. This mouse, along with the Cr1/2KO, will be a critical tool in delineating Cr1 specific immune response effects.

Familial Predisposition to Monoclonal Gammopathy of Unknown Significance, Waldenström's Macroglobulinemia, and Multiple Myeloma

The medical literature contains reports of around 130 families with two or more cases of MM, MGUS, or WM. An Icelandic family with multiple cases of MGUS, WM, and lymphoma was first described in 1978. In vitro testing of peripheral blood lymphocytes revealed increased production of immunoglobulins in response to poke-weed mitogen in 10 out of 35 family members, referred to as hyperresponders (HR). Enhanced B-cell survival after stimulation was associated with prolonged expression of Bcl-2. A population-based cancer registry study of 218 MM patients identified 7 additional families. Nine new cases of monoclonal gammopathy were detected by the screening of 350 family members. Further testing confirmed previously identified HR in the originally described family as well as detecting new cases. Only two HR were found in the recently identified families. The long-term aim is to identify the genetic background(s) and biology predisposing to the emergence of a persistent clone of immunoglobulin-producing cells.

Cord blood B cells are mature in their capacity to switch to IgE-producing cells in response to interleukin-4 in vitro

Neonatal B cells have been considered immature because of their impaired capacity to produce immunoglobulins in response to polyclonal activators in vitro. Here we demonstrate that cord blood mononuclear cells (MNC) produce normal levels of IgE in vitro when cultured in the presence of interleukin-4 (IL-4), indicating that the B cells are mature in their capacity to switch to IgE-producing cells. However, in contrast to adult peripheral blood T cells, cord blood T cells failed to produce detectable levels of IL-4 upon activation by phytohaemagglutinin (PHA) concanavalin A (Con A) or combinations of PHA and the phorbol ester TPA. Interferon-gamma (IFN-gamma) production by cord blood T cells following activation by Con A or PHA was also strongly reduced. However, high levels of IFN-gamma, significantly higher than those produced by adult T cells, were synthesized in response to combinations of PHA and TPA, indicating that IFN-gamma production by cord blood T cells is not intrinsically defective. In contrast, cord blood T cells produced levels of IL-2 that were significantly higher than those obtained by adult T cells tested in parallel. Collectively, our data indicate that the minimal levels of IgE production measured in cord blood (less than 1 U/ml) are not due to immaturity of the cord blood B cells, but may be associated with the failure of cord blood T cells to produce detectable levels of IL-4, which has been shown to be responsible for induction of IgE synthesis both in vitro and in vivo.

Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells

The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4− memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4+ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.

Role of polymorphonuclear leukocytes, nitric oxide synthase, and cyclooxygenase in vascular permeability changes induced by C5a agonist peptides

Tumor responses to radioimmunotherapy combined with peptide agonists of human C5a anaphylatoxin such as GCGYSFKPMPLaR (C5aAP) are two- to four-fold better, depending on the dose of C5aAP, than responses to radioimmunotherapy alone. The enhanced tumor vascular permeability (VP) is the key factor responsible for this improvement. These studies were designed to identify the sequence of events leading to the improved extravasation of immunoglobulin in response to C5aAP. The VP changes were measured in mice after administration of C5aAP alongside of various mediators. The depletion of circulating polymorphonuclear neutrophils (PMN) in mice abolished the C5aAP-induced VP increase. Blocking of P-selectin also returned VP to its basal levels after the C5aAP treatment, indicating that C5aAP-induced VP changes are initiated by interactions of C5aAP with PMNs. Aminoguanidine, an inducible nitric oxide synthase (NOS) inhibitor, given before C5aAP returned VP to control levels. N(omega)-nitro-L-arginine methyl ester, a nonselective NOS inhibitor, had a marginal effect on the activity of C5aAP. Indomethacin, a nonselective cyclooxygenase inhibitor, suppressed C5aAP-induced increases in VP, whereas N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide, a selective cyclooxygenase-2 inhibitor, was active only at high doses. While C5aAP given i.p. did not alter tumor uptake of (125)I-B72.3, the i.v. administration resulted in approximately 40% increase, confirming the prerequisite interaction of C5aAP with PMNs. The sequence leading to the increased VP appears to be initiated by the interaction of C5aAP with C5a receptor expressed on PMNs followed by binding to endothelial cells of blood vessels. The interaction with P-selectin is responsible for the initiation of the nitric oxide cascade as evidenced by inducible NOS activation. Additionally, prostaglandins are required for expression of the full magnitude of the C5aAP activities.

Modulation of B-lymphocyte and NK cell activities by glycoinositolphospholipid purified from Trypanosoma cruzi.

Glycoinositolphospholipids (GIPLs) are some of the major glycolipids of the Trypanosoma cruzi surface that were previously shown to activate B cells. In the present study, we investigated whether (i) T. cruzi GIPLs could induce immunoglobulin secretion from B cells in the absence of T cells and NK cells and whether (ii) NK cells are also stimulated by the GIPLs. B cells purified from mice deficient in both T and NK cells (CD3epsilon transgenic mice) secreted immunoglobulin in response to the GIPL. This response was increased by coculture with a murine NK cell line. The T. cruzi GIPL also increased the NK cell (interleukin-2 induced) proliferative response. Our data indicate that the T. cruzi GIPL has a direct stimulatory effect on NK cells and induces immunoglobulin secretion in the absence of T lymphocytes and NK cells. These findings suggest that this T. cruzi-derived molecule may be one of the stimulators that lead to NK cell activation during T. cruzi infection.

Enhanced Immunoglobulin Formation of Immortalized B Cells From Hypertensive Patients

Increased immunoglobulin levels and leukocyte counts have frequently been reported in essential hypertension. The underlying mechanisms, however, have remained obscure. Enhanced Na(+)-H+ exchanger activity is another frequently observed abnormality in essential hypertension that persists in immortalized B lymphoblasts and coincides with enhanced proliferation. We investigated the capacity of B lymphoblasts from essential hypertensive patients to synthesize and secrete immunoglobulins. Six B cell lines from essential hypertensive patients with enhanced Na(+)-H+ exchanger phenotype and six cell lines from normotensive subjects were studied. Lymphocyte markers were visualized by immunostaining. Immunoglobulin secretion was analyzed by enzyme-linked immunosorbent assay. These cell lines did not differ with respect to B cell markers. In response to 100 nmol/L platelet-activating factor, cells from hypertensive patients proliferated distinctly more quickly and their cell number increased by 3.9 +/- 0.4-fold (mean +/- SD) within 4 days, whereas the number of cells from normotensive subjects increased by only 2.6 +/- 0.1-fold. Furthermore, platelet-activating factor induced average increases in IgM and IgG formation of 13.3- and 5.4-fold, respectively, in lymphoblasts from hypertensive patients, which was significantly higher than increases in cells from normotensive subjects (1.4- and 1.2-fold, respectively). Thus, lymphoblasts from hypertensive patients proliferate more quickly and secrete more immunoglobulins in response to a physiological stimulus in vitro. This may contribute to the raised immunoglobulin levels and leukocyte counts reported in vivo.

Cross‐linking of surface IgM, but not surface IgD receptors, by soluble monoclonal antibodies primes murine B cells to secrete immunoglobulin in response to lymphokines

We have previously reported the development of a two-step culture system in which soluble anti-mu monoclonal antibodies prime small resting murine B cells to secrete immunoglobulin (Ig) in response to restimulation with a mixture of interleukin-4 (IL-4) and IL-5. Here we have extended these studies to investigate the effects of engaging surface IgD (sIgD). We find that, unlike anti-mu, three different anti-delta monoclonal antibodies did not prime B cells to secrete Ig. In addition, these anti-delta antibodies inhibited anti-mu-stimulated priming for Ig secretion, while enhancing DNA synthesis in response to anti-mu. Furthermore, anti-delta antibodies still inhibited anti-mu-induced priming when added 24-48 h after anti-mu. These results therefore suggest that triggering of sIgD on B cells induces a dominant inhibitory signal which is not necessarily dependent upon co-ligation of sIgM and sIgD receptors. In addition, these findings raise the possibility that ligating sIgM or sIgD receptors on mature B cells in the absence of T cell help, may produce different downstream effects.

Soluble anti-mu monoclonal antibodies prime resting B cells to secrete immunoglobulins in response to interleukins-4 and -5.

Soluble anti-immunoglobulin (Ig) antibodies have been generally found to inhibit Ig secretion in B cells, via largely unknown mechanisms. To investigate this phenomenon further a two-step culture system was used in which B cells are primed for 24-72 h with various soluble monoclonal or polyclonal anti-Ig antibodies: after washing the cells were placed in readout cultures with a combination of interleukin (IL)-5 and IL-4. Using this protocol B cells primed with (mitogenic or nonmitogenic) anti-mu monoclonal antibodies differentiated into large numbers of IgM-secreting cells, comparable to responses to lipopolysaccharide. In contrast, priming with polyclonal rabbit anti-Ig or monoclonal anti-kappa antibodies, markedly inhibited Ig secretion induced by IL-4 + IL-5. In addition, anti-mu was markedly inhibitory if left in the readout cultures with the two lymphokines. These results, therefore, indicate that appropriate cross-linking of surface IgM receptors on B cells can prime the cells to secrete Ig when they are restimulated by T cell-derived lymphokines in the absence of anti-mu. In contrast co-ligation of both surface IgM and surface IgD receptors apparently results in powerful inhibition of Ig secretion, which is not reversed by stimulation with IL-4 plus IL-5.

Altered Humoral Immunoregulation During Human Pregnancy

The in vitro production of immunoglobulins in response to stimulation with pokeweed mitogen (PWM) and fixed/killed Staphylococcus aureus Cowan 1 (SAC) was measured in conjunction with in vivo assays of plasma immunoglobulin levels to examine the quality and quantity of humoral immunity during human pregnancy and at parturition. Following stimulation with PWM, there is a significant enhancement of in vitro immunoglobulin-G (IgG) production during pregnancy. Following stimulation with PWM and SAC, there was a significant reduction in in vitro immunoglobulin-M (IgM) production immediately following parturition. There was a significant decrease in the plasma levels of IgG during pregnancy, although no change in the plasma levels of IgM were observed. The decrease in plasma immunoglobulin levels during pregnancy cannot be explained as the result of hemodilution and transplacental transfer. Altered humoral immunoregulation is the most likely means whereby an increase in immunoglobulin production during human pregnancy could occur. The possible effects of this on the outcome of pregnancy are discussed.

Antigen-Driven Immunoglobulin Production by Human Colostral Lymphocytes

It has long been recognized that human milk contains substantial quantities of secretory IgA which is elaborated by plasma cells located proximal to the ductal epithelium. The presence of lymphocytes, granulocytes and macrophages in the milk itself raises the question of whether these "shed" milk cells might potentially serve a function with regard to protecting the suckling neonate from infection. The functionality of milk B-lymphocytes has remained particularly controversial. In this report, we describe the use of a novel technique of milk cell separation prior to cell culture and demonstrate the ability of colostral B-lymphocytes to elaborated immunoglobulin in response to antigenic stimulation using vaccine strain polio virus.