Rabbits preferentially rearrange the 3’-most VH gene segment during VDJ gene rearrangement. Early in life, rabbit B cells diversify these VDJ genes in gut-associated lymphoid tissue (GALT) in response to signals acquired from intestinal commensal bacteria, and thus generate a diversified primary antibody repertoire. To gain insight into the cell-cell and cell-microbe interactions required for VDJ gene diversification, we examined B cell surface expression levels of four chemokine receptors that mediate trafficking to important sites within GALT during repertoire diversification. We stained B cells from two- through seven-day-old appendix with fluorescence-labeled Ig-fusion proteins of the chemokines CXCL12, CCL20, CXCL13 and CCL21 and analyzed them by flow cytometry. The changes we observed in relative chemokine receptor expression levels during the first week of life suggest a model in which B cells, upon entering appendix follicles, first traffic to the follicle-associated epithelium, where they likely encounter commensal bacteria sampled from the intestinal microbiota. B cells subsequently migrate to, and likely receive additional signals from, the follicular dendritic cell network. Upon becoming activated, B cells then traffic to the basal region of the follicle, where they proliferate and diversify their VDJ genes, thereby generating the primary antibody repertoire.
- Copyright © 2011 by The American Association of Immunologists, Inc.