Diversification of the primary antibody repertoire begins during early follicle development in the rabbit appendix

作者：Zhai Shi Kang; Lanning Dennis K^*

来源：Molecular Immunology, 2013, 54(2): 140-147.

DOI：10.1016/j.molimm.2012.11.010

• Activation-induced cytidine deaminase
• B cell proliferation
• Gut-associated lymphoid tissue (GALT)
• Intestinal commensals
• Intestinal microbiota
• Rabbit appendix

Rabbits generate a diversified primary antibody repertoire by somatically mutating, in gut-associated lymphoid tissue (GALT), an initial repertoire that is limited by preferential rearrangement of the 3%26apos;-most IGVH gene segment. To determine when repertoire diversification begins in GALT, we performed in situ hybridization on neonatal rabbit appendix sections with an activation-induced cytidine deaminase (AID) riboprobe, because AID is required for the mutational processes that diversify the primary antibody repertoire. We first detected AID mRNA expression around 1 week of age, in the basal region of developing follicles. By PCR-amplifying V-D-J genes from AID mRNA(+) B cells isolated by laser capture microdissection, we found evidence of somatic hypermutation, and one likely instance of somatic gene conversion. Our results suggest that V-(D)-J gene diversification begins during early postnatal appendix development, in B cells stimulated to enter a proliferative program by signals derived from select intestinal commensals.

• 出版日期2013-6