|
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. |
