Numbers Of IgA-producing Plasma Cells Research Articles

Early supplementation of Saccharomyces cerevisiae boulardii CNCM I-1079 in newborn dairy calves increases IgA production in the intestine at 1 week of age

The early development of immunity and microbiota in the gut of newborn calves can have life-long consequences. Gut microbiota and the intestinal barrier interplay after birth, establishing a homeostatic state whereby mucosal cells cohabit with microorganisms to develop a healthy gut. We hypothesized that postnatal codevelopment of gut immunity and microbiota could be influenced by early-life supplementation with live yeast. Starting from birth, calves either received a daily supplementation of Saccharomyces cerevisiae boulardii CNCM I-1079 (SCB, 10 × 109 cfu/d, n = 10) in the morning meal for 7 d or no supplementation (n = 10). Each animal received 2 adequate colostrum replacer meals at 2 and 12 h of life (expected total IgG fed = 300 g) before being fed milk replacer twice a day. Passive transfer of immunity (total protein, IgG, and IgA) through colostrum was evaluated and endogenous production of IgA was investigated by measuring IgA-producing plasma cells, IgA relative gene expression (PIGR and CD79A), and secretory IgA concentration in the gut. The concentration of targeted microbial groups was evaluated with quantitative PCR in the gut digesta collected at d 7 of life. Early SCB supplementation did not impair immunoglobulin absorption and all calves had successful passive transfer of immunity (serum IgG concentration >15 mg/mL at d 1 and d 7 of age). Although the expression of IgA relative gene expression (PIGR and CD79A) was not different, SCB calves had higher secretory IgA concentrations in the ileum (1.98 ± 0.12 mg/g of dry matter; DM) and colon (1.45 ± 0.12 mg/g of DM) digesta compared with control animals (1.18 and 0.59 ± 0.12 mg/g of DM, respectively). In addition, the number of IgA-producing plasma cells were greater in both ileum (2.55 ± 0.40 cells/mm2) and colon (3.03 ± 0.40 cells/mm2) tissues for SCB calves compared with control (respectively 1.00 ± 0.40 and 0.60 ± 0.42 cells/mm2). Endogenous IgA production in the gut of SCB calves was enhanced, which could make them less prone to pathogen intrusion. In addition, SCB calves had higher Lactobacillus and tended to have higher Faecalibacterium prausnitzii in the jejunum compared with control calves, which suggests that SCB supplementation during early-life gut colonization may have a positive effect in newborn calves. Direct SCB supplementation or the cross-talk between SCB and bacteria may be responsible for stimulating IgA production and may play a key role in shaping early colonization in the gut of newborn calves.

Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism.

Enhancement of intestinal IgA responses is a primary strategy in the development of oral vaccine. Dietary fatty acids are known to regulate host immune responses. In this study, we show that dietary palmitic acid (PA) and its metabolites enhance intestinal IgA responses. Intestinal IgA production was increased in mice maintained on a PA-enriched diet. These mice also showed increased intestinal IgA responses against orally immunized Ag, without any effect on serum Ab responses. We found that PA directly stimulates plasma cells to produce Ab. In addition, mice receiving a PA-enriched diet had increased numbers of IgA-producing plasma cells in the large intestine; this effect was abolished when serine palmitoyltransferase was inhibited. These findings suggest that dietary PA regulates intestinal IgA responses and has the potential to be a diet-derived mucosal adjuvant.

Lymphocyte homing and Ig secretion in the murine mammary gland.

In mice the majority of the immunoglobulins (Ig) in milk belongs to the IgA class. Prior to its transepithelial transportation into the milk, dimeric IgA (dIgA) is bound to the transmembrane form of the secretory component or polymeric Ig receptor (SC/pIgR). The latter is synthesized in the epithelial cells lining the ducts and alveoli of the mammary gland. A candidate for playing the role of adhesion molecule to primed lymphocytes present in the murine mammary gland might be the mucosal addressin cell adhesion molecule-1 (MAdCAM-1). We studied the correlation between the levels of IgA in colostrum and milk, the number of IgA producing plasma cells in the mammary gland and the expression of MAdCAM-1 in mammary gland endothelial cells during pregnancy and lactation. The relation between the IgA levels in the milk and the expression levels of pIgR in mammary gland epithelial cells was also investigated. We found that the expression of MAdCAM-1 and pIgR starts in early-mid pregnancy; the number of IgA-producing plasma cells and the IgA concentration in milk increase from early lactation onwards. The MAdCAM-1 expression declines during lactation whereas the pIgR levels and IgA-producing plasma cell numbers rise until the end of lactation. Because the MAdCAM-1 level starts to rise several days before the rise of the IgA-producing plasma cell level, MAdCAM-1 cannot be the rate determining factor governing extravasation of primed B cells to the mammary gland. We also conclude that the pIgR is present in sufficient amounts to enable increasing S-IgA secretion into the milk during lactation.

Clonal Expansion of CD4+ TCRββ+ T Cells in TCR α-Chain- Deficient Mice by Gut-Derived Antigens

AbstractA population of CD4+ α−β+ T cells increases in the mucosal and peripheral lymphoid tissues of TCRα-chain-deficient mice with inflammatory bowel disease. The α−β+ T cells, which produce predominantly IL-4, mediate the proliferation of colonic epithelial crypts and the infiltration of large numbers of IgA-producing plasma cells into the lamina propria of the colon. To examine whether enteric Ags were recognized by a population of monoclonal α−β+ T cells leading to the intestinal inflammation, we examined the usage and clonotypes of TCR expressed by the α−β+ T cells in TCRα-chain-deficient mice with inflammatory bowel disease. Analyses of immunoprecipitates by two dimensional electrophoresis and single-cell RT-PCR revealed that TCR of the α−β+ T cells was a homodimer of β-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR Vβ transcripts revealed monoclonal accumulation of the α−β+ T cells in the colonic lamina propria of the diseased mice. DNA sequencing revealed the accumulation of the α−β+ T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4+ α−β+ T cells expressing a homodimeric form of the TCRβ-chains can be clonally expanded upon the stimulation with gut-derived Ags.

Effects of chronic alcohol abuse on duodenal mononuclear cells in man.

The aim of this study was to investigate whether chronic alcohol abuse alters the number and distribution of mononuclear cells of the duodenal mucosa. The number of common leukocyte antigen (CLA)-positive interepithelial lymphocytes (IEL), B lymphocytes (BL), IgA-producing plasma cells (IgA-PC), and macrophages (MP) was quantitatively evaluated in biopsies of the duodenal mucosa of patients with alcohol abuse compared to subjects without alcohol abuse. Biopsies from the descending part of the duodenum were obtained by endoscopy from two groups of patients with chronic alcohol abuse (group A1, abstinence <5 days, N = 21) and group A2 abstaining 5-10 days (N = 6). Twenty-five subjects without alcohol abuse served as controls (C). Immunohistochemical staining was done by avidin-biotin-complex method. In addition, the content of IgA in the plasma cells was determined by using a TV-densitometric method. The number of B-lymphocytes in the lamina propria was increased by 37% in group A1 (P < 0.005). A distinct decrease was observed in group A1 compared to C in the number of IEL that were CLA positive (-50%, P < 0.025) and in the number of macrophages (-54%, P < 0.025). In group A2 the differences in the number of B lymphocytes and macrophages were no longer seen. In A1, there was no significant change in the number of IgA-producing plasma cells or in the number of interepithelial lymphocytes counted after H&E staining compared to the controls. There was no difference in content of IgA in the IgA-producing plasma cells. From these results it is concluded that chronic alcohol abuse significantly influences the gut-associated immune system, possibly by increasing the permeability of the gut mucosa to macromolecules that act as antigens.

Gut permeability, intestinal morphology, and nutritional depletion.

Nutritional depletion increases the risk for postoperative complications. The intestinal barrier may be important in the underlying pathophysiologic mechanism. In this study, 26 patients were evaluated to determine whether nutritional depletion was related to gut integrity and intestinal morphology. Nutritional depletion was estimated by calculating percentage ideal body weight (PIB) or percentage ideal fat free mass (PIFFM). To assess gut integrity, a lactulose/mannitol (L/M) test was performed. Duodenal biopsies were taken, and villous height, crypt depth, number of IgA-producing plasma cells, intraepithelial lymphocytes (IELs), and proliferating index were determined. The L/M ratio was increased, and villous height was decreased in depleted patients. Depletion was not associated with differences in the number of immune cells or proliferating index. The number of IgA-producing plasma cells was positively correlated with the L/M ratio. This study shows that nutritional depletion is associated with increased intestinal permeability and a decrease in villous height.

Acinar cell basal-lateral membrane-endomembrane traffic may mediate interactions with both T cells and B cells.

The lacrimal glands are normally populated by significant numbers of IgA-producing plasma cells and T lymphocytes, with CD8 cells in twofold excess over CD4 cells. The numbers of these cells increase during normal aging, and there has been speculation that they may exacerbate the lacrimal dysfunction of primary lacrimal deficiency. Lymphocytic infiltration increases much more dramatically in Sjögren’s syndrome, an immune system disorder in which CD4 cells dominate the T lymphocyte population, and the antibody-producing population includes large numbers of B cells. The B cell infiltrates are polyclonal and often produce IgG and IgM against intracellular antigens, such as the ribonuclear proteins Ro and La and a variety of Golgi proteins. Because of the severity of the ocular surface disease and the debilitating and potentially life-threatening nature of the systemic manifestations of Sjögren’s syndrome, it is important to identify the mechanisms that lead to CD4 cell and B cell proliferation in the lacrimal glands.KeywordsAcinar CellGolgi ComplexLacrimal GlandOcular Surface DiseaseMembrane RecyclingThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

IgA production by peritoneal cavity B cells is IL‐6 independent: Implications for intestinal IgA response

We have shown previously both in vitro and in vivo that IL-6 is an important factor for the development of IgA-producing B cells. However, despite the lack of this cytokine in mice with targeted disruption of the interleukin (IL)-6 gene (gene knockout mice), a substantial number of IgA-producing plasma cells occur in their intestinal mucosa. The experiments reported here indicate that there is a population of IgA-producing B cell precursors originating from the peritoneal cavity, distinguished from conventional Peyer's patch-derived precursors by their expression of CD5, and that IgA secretion by these cells is IL-6-independent. Further, there is an increase in CD5 expression among brightly staining IgA-producing cells obtained from the intestinal lamina propria of IL-6 gene-disrupted mice compared to normal controls. These data suggest an explanation for the persistence of IgA-producing plasma cells in the intestinal mucosa of IL-6-depleted mice and indicate the importance of IL-6 for development of conventional precursors of IgA-producing B cells, but not those derived from the peritoneal cavity pool.