Role of the Intestinal Microflora in Galtgc Responses

Commensal bacteria are essential to induce GALT GC responses and to promote both antigen-specific and natural IgA antibody titers. Germ-free animals lack spontaneous GCs in PP and in other GALT sites, and IgA antibody titers are strongly diminished in these mice (Shroff and Cebra 1995). Colonization of the gut of germ-free mice with a single commensal strain leads to a rapid induction of GALT GC responses resulting in a vigorous IgA antibody response (Talham et al. 1999). The molecular mechanisms responsible for the induction of GALT GCs by the intestinal microflora are still largely unknown,

Fig. 3 Spontaneous GCs in PP of three independent BCR transgenic mice as revealed by flow cytometric analyses. Shown are CD19+ gated B cells. Percentages ofboxed GC B cells within the CD19+ B cell gate are indicated although BCR-mediated antigen recognition of bacterial antigens has been suggested.

To test the latter hypothesis, we studied the contribution of commensal bacteria to GALT GC responses of BCR-deficient LMP2A mice. Specifically, 3-week old LMP2A mice received for 2 weeks in the drinking water a cocktail of antibiotics against a spectrum of both aerobic and anaerobic Gr+ and Gr- bacteria. Flow cytometric analysis of single-cell suspensions from PP and MLN of LMP2A mice revealed a significant and selective reduction in the fraction of GC B cells in treated animals, compared with their littermate controls kept on antibiotic-free water (Casola et al. 2004). These results suggest that GCs in GALT of LMP2A mice are, as in wild-type animals, dependent on the presence of the intestinal microflora. Thus we conclude that bacterial stimulation can recruit B cells into GALT GCs irrespective of their BCR specificity, possibly through the engagement of innate immune receptors. A similar mechanism may also account for the induction of GC responses in the rabbit appendix undergoing primary diversification of the antibody repertoire as a result of postnatal encounter with commensal bacteria of the intestinal flora (Rhee et al. 2004).

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