Abstract
In conventionally reared mice germinal centers (GCs) are chronically induced in Peyer’s patches (PP), mesenteric lymph node (MLN), and isolated lymphoid follicles (ILF) of gut-associated lymphoid tissues (GALT), as a result of continuous B cell stimulation by commensal bacteria. It is generally thought that BCR-mediated antigen recognition controls the recruitment and thus selection of B cells within GALT GCs. However, recent results challenge this view and suggest that engagement of innate immune receptors by microbial antigens promotes B cell recruitment to, and maintenance within, the GC, irrespective of BCR specificity. We propose a scenario in which microbial determinants presented by follicular dendritic cells (FDCs) to innate receptors on B cells within the GC support the survival and concomitant expansion of somatically mutated, IgA-class-switched B cell clones expressing a variety of BCR specificities. From this pool, B cell mutants recognizing gut-derived antigens through their BCR are either, in GCs, drawn into the process of affinity maturation, or, in the lamina propria (LP) of the gut, locally selected to differentiate into plasmablasts, thus contributing to the continuous production of IgA antibodies required for an efficient protection against commensal and pathogenic microorganisms.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Akira S, Takeda K (2004). Toll-like receptor signalling. Nat Rev Immunol 4, 499–511.
Becker RS, Knight KL (1990). Somatic diversification of immunoglobulin heavy chain VDJ genes: evidence for somatic gene conversion in rabbits. Cell 63, 987–997.
Bos NA, Bun JC, Popma SH, Cebra ER, Deenen GJ, van der Cammen MJ, Kroese FG, Cebra JJ (1996). Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both germ line and somatically mutated VH genes and is reactive with commensal bacteria. Infect Immun 64, 616–623.
Brigl M, Brenner MB (2004). CD1: antigen presentation and T cell function. Annu Rev Immunol 22, 817–890.
Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB (2003). Mechanism of CD1d-restricted natural killer T cell activation duringmicrobial infection. Nat Immunol 4, 1230–1237.
Caldwell RG, Wilson JB, Anderson SJ, Longnecker R (1998). Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9, 405–411.
Casola S, Otipoby KL, Alimzhanov M, Humme S, Uyttersprot N, Kutok JL, Carroll MC, Rajewsky K (2004). B cell receptor signal strength determines B cell fate. Nat Immunol 5, 317–327.
Cazac BB, Roes J (2000). TGF-β receptor controls B cell responsiveness and induction of IgA in vivo. Immunity 13, 443–451.
Cebra JJ (1999). Influences of microbiota on intestinal immune system development. Am J Clin Nutr 69, 1046S–1051S.
Craig SW, Cebra JJ (1971). Peyer’s patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med 134, 188–200.
Fagarasan S, Kinoshita K, Muramatsu M, Ikuta K, Honjo T (2001). In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413, 639–643.
Fagarasan S, Shinkura R, Kamata T, Nogaki F, Ikuta K, Honjo T (2000). Mechanism of B1 cell differentiation and migration in GALT. Curr Top Microbiol Immunol 252, 221–229.
Fruehling S, Longnecker R (1997). The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology 235, 241–251.
Husband AJ, Gowans JL (1978). The origin and antigen-dependent distribution of IgA-containing cells in the intestine. J Exp Med 148, 1146–1160.
Kaser A, Nieuwenhuis EE, Strober W, Mayer L, Fuss I, Colgan S, Blumberg RS (2004). Natural killer T cells in mucosal homeostasis. Ann N Y Acad Sci 1029, 154–168.
Kearney JF, Lawton AR (1975). B lymphocyte differentiation induced by lipopolysaccharide. I. Generation of cells synthesizing four major immunoglobulin classes. J Immunol 115, 671–676.
Koni PA, Flavell RA (1999). Lymph node germinal centers form in the absence of follicular dendritic cell networks. J Exp Med 189, 855–864.
Kraehenbuhl JP, Neutra MR (1992). Transepithelial transport and mucosal defence II: secretion of IgA. Trends Cell Biol 2, 170–174.
Kraus M, Alimzhanov MB, Rajewsky N, Rajewsky K (2004). Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer. Cell 117, 787–800.
Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM(1995). CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546–549.
Kroese FG, Butcher EC, Stall AM, Lalor PA, Adams S, Herzenberg LA (1989). Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity. Int Immunol 1, 75–84.
Kronenberg M (2004). Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol.
Lanning D, Zhu X, Zhai SK, Knight KL (2000). Development of the antibody repertoire in rabbit: gut-associated lymphoid tissue, microbes, and selection. Immunol Rev 175, 214–228.
MacLennan IC (1994). Germinal centers. Annu Rev Immunol 12, 117–139.
Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM (2000). A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288, 2222–2226.
Macpherson AJ, Uhr T (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662–1665.
Madsen L, Labrecque N, Engberg J, Dierich A, Svejgaard A, Benoist C, Mathis D, Fugger L (1999). Mice lacking all conventional MHC class II genes. ProcNatl Acad Sci USA 96, 10338–10343.
Mattner J, Debord KL, Ismail N, Goff RD, Cantu C, 3rd, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin, N., et al. (2005). Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525–529.
Miller CL, Burkhardt AL, Lee JH, Stealey B, Longnecker R, Bolen JB, Kieff E (1995). Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity 2, 155–166.
Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000). Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102, 553–563.
Pospisil R, Mage RG (1998). Rabbit appendix: a site of development and selection of the B cell repertoire. Curr Top Microbiol Immunol 229, 59–70.
Rajewsky K (1996). Clonal selection and learning in the antibody system. Nature 381, 751–758.
Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2, 361–367.
Reynaud CA, Anquez V, Grimal H, Weill JC (1987). A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell 48, 379–388.
Reynaud CA, Bertocci B, Dahan A, Weill JC (1994). Formation of the chicken B-cell repertoire: ontogenesis, regulation of Ig gene rearrangement, and diversification by gene conversion. Adv Immunol 57, 353–378.
Reynaud CA, Mackay CR, Muller RG, Weill JC (1991). Somatic generation of diversity in a mammalian primary lymphoid organ: the sheep ileal Peyer’s patches. Cell 64, 995–1005.
Reynaud CA, Weill JC (1996). Postrearrangement diversification processes in gutassociated lymphoid tissues. Curr Top Microbiol Immunol 212, 7–15.
Rhee KJ, Jasper PJ, Sethupathi P, Shanmugam M, Lanning D, Knight KL (2005). Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues. J ExpMed 201, 55–62.
Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL (2004). Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 172, 1118–1124.
Sangster MY, Riberdy JM, Gonzalez M, Topham DJ, Baumgarth N, Doherty PC (2003). An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions. J Exp Med 198, 1011–1021.
Shikina T, Hiroi T, Iwatani K, Jang MH, Fukuyama S, Tamura M, Kubo T, Ishikawa H, Kiyono H (2004). IgA class switch occurs in the organized nasopharynx-and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut. J Immunol 172, 6259–6264.
Shroff KE, Cebra JJ (1995). Development of mucosal humoral immune responses in germ-free (GF) mice. Adv ExpMed Biol 371A, 441–446.
Shroff KE, Meslin K, Cebra JJ (1995). Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect Immun 63, 3904–3913.
Stoel M, Jiang HQ, van Diemen CC, Bun JC, Dammers PM, Thurnheer MC, Kroese FG, Cebra JJ, Bos NA(2005). Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts. J Immunol 174, 1046–1054.
Talham GL, Jiang HQ, Bos NA, Cebra JJ (1999). Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infect Immun 67, 1992–2000.
Thompson CB, Neiman PE (1987). Somatic diversification of the chicken immunoglobulin light chain gene is limited to the rearranged variable gene segment. Cell 48, 369–378.
Thorley-Lawson DA (2001). Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1, 75–82.
Thurnheer MC, Zuercher AW, Cebra JJ, Bos NA (2003). B1 cells contribute to serum IgM, but not to intestinal IgA, production in gnotobiotic Ig allotype chimeric mice. J Immunol 170, 4564–4571.
Treiner E, Duban L, Moura IC, Hansen T, Gilfillan S, Lantz O (2005). Mucosal-associated invariant T (MAIT) cells: an evolutionarily conserved T cell subset. Microbes Infect, in press.
Vajdy M, Kosco-Vilbois MH, Kopf M, Kohler G, Lycke N (1995). Impaired mucosal immune responses in interleukin 4-targeted mice. J Exp Med 181, 41–53.
Walport MJ (2001). Complement. First of two parts. N Engl J Med 344, 1058–1066.
Weinstein PD, Anderson AO, Mage RG (1994). Rabbit IgH sequences in appendix germinal centers: VH diversification by gene conversion-like and hypermutation mechanisms. Immunity 1, 647–659.
Weinstein PD, Schweitzer PA, Cebra-Thomas JA, Cebra JJ (1991). Molecular genetic features reflecting the preference for isotype switching to IgA expression by Peyer’s patch germinal center B cells. Int Immunol 3, 1253–1263.
Weltzin R, Lucia-Jandris P, Michetti P, Fields BN, Kraehenbuhl JP, Neutra MR (1989). Binding and transepithelial transport of immunoglobulins by intestinal M cells: demonstration using monoclonal IgA antibodies against enteric viral proteins. J Cell Biol 108, 1673–1685.
Zhou D, Mattner J, Cantu C, 3rd, Schrantz N, Yin N, Gao Y, Sagiv Y, Hudspeth K, Wu YP, Yamashita T, et al. (2004). Lysosomal glycosphingolipid recognition by NKT cells. Science 306, 1786–1789.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Casola, S., Rajewsky, K. (2006). B Cell Recruitment and Selection in Mouse GALT Germinal Centers. In: Honjo, T., Melchers, F. (eds) Gut-Associated Lymphoid Tissues. Current Topics in Microbiology and Immunology, vol 308. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-30657-9_7
Download citation
DOI: https://doi.org/10.1007/3-540-30657-9_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-30656-6
Online ISBN: 978-3-540-30657-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)