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Early in life, vertebrates must generate a diverse primary antibody repertoire to provide protection from pathogens. The strategies for accomplishing this, however, differ among vertebrate species. In rabbits, preferential use of one V gene during V-D-J gene rearrangement in the bone marrow produces an initial antibody repertoire of limited diversity. This initial repertoire is extensively diversified by somatic gene conversion and somatic hypermutation in gut-associated lymphoid tissues (GALT). In a striking example of the intestinal microbiota’s impact on host development, diversification of the primary antibody repertoire in GALT is completely dependent on select intestinal commensal bacteria. My research is focused on understanding the host-microbial interactions that generate the primary antibody repertoire. B cells begin entering GALT two days after birth, and we found that antibody repertoire diversification begins by the end of the first week of life. By studying B cell trafficking within GALT follicles during the first week of life, we can therefore gain insight into the microbial and host cell interactions that stimulate B cells to diversify their V-D-J genes. For these studies, we identified regional chemokine expression in GALT, and monitor changes in chemokine receptor expression on B cells by flow cytometry. These studies will determine the sites B cell traffic to within GALT follicles and thus identify the host and microbial interactions that stimulate diversification of the primary antibody repertoire. |
