Diversified bursal medullary B cells survive and expand independently after depletion following neonatal infectious bursal disease virus infection

SummaryThe primary immunoglobulin repertoire of chickens is generated not by gene rearrangement but by a subsequent process of gene conversion in proliferating immature B cells within the follicles of a specialized gut‐associated lymphoid organ, the bursa of Fabricius. Neonatal infection with infectious bursal disease virus can eliminate almost the entire bursal B‐cell compartment. Thereafter, two types of follicle reappear. Larger follicles, with rapidly proliferating B cells and normal structure, are correlated with partial recovery of antibody response. Smaller follicles, lacking distinct cortex and medulla, appear unable to produce antigen‐responsive B cells. To understand the genesis of the two types of follicle, we analysed their VL sequences and activation‐induced deaminase mRNA levels. The results provide a model of bursal repopulation in which surviving bursal stem cells generate new follicles with normal morphology and function, while surviving medullary B cells continue to proliferate slowly, under the influence of stromal cells, giving rise to the smaller follicles. The latter remain fixed in a stage of development incapable of further gene diversification.