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

The 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.