Chemokine-mediated B cell trafficking during early rabbit GALT development.
Microbial and host cell interactions stimulate rabbit B cells to diversify the primary Ab repertoire in GALT. B cells at the base of appendix follicles begin proliferating and diversifying their V-(D)-J genes around 1 wk of age, ∼5 d after B cells first begin entering appendix follicles. To gain insight into the microbial and host cell interactions that stimulate B cells to diversify the primary Ab repertoire, we analyzed B cell trafficking within follicles during the first week of life. We visualized B cells, as well as chemokines that mediate B cell homing in lymphoid tissues, by in situ hybridization, and we examined B cell chemokine receptor expression by flow cytometry. We found that B cells were activated and began downregulating their BCRs well before a detectable B cell proliferative region appeared at the follicle base. The proliferative region was similar to germinal center dark zones, in that it exhibited elevated CXCL12 mRNA expression, and B cells that upregulated CXCR4 mRNA in response to signals acquired from selected intestinal commensals localized in this region. Our results suggest that after entering appendix follicles, B cells home sequentially to the follicle-associated epithelium, the follicular dendritic cell network, the B cell/T cell boundary, and, ultimately, the base of the follicle, where they enter a proliferative program and diversify the primary Ab repertoire.
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Shi-Kang
SK
Zhai
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Veronica V
VV
Volgina
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Periannan
P
Sethupathi
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Katherine L
KL
Knight
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153 dlannin@luc.edu.
Dennis K
DK
Lanning
D000818:Animals; D000831:Animals, Newborn; D001065:Appendix / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008954:Models, Biological; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase