2 DISTINCT PATHWAYS OF B-CELL DEVELOPMENT IN PEYERS-PATCHES

The developmental biology of sheep ileal and jejunal Peyer's patches ( PP) was investigated using corticosteroids to deplete immature B lymph ocytes. During a 7-day treatment with dexamethasone, ileal PP follicul ar (iPf)B-cell proliferation was arrested and most iPfB-cells died. Th is resulted in follicular involution with the survival of mesenchymal cells. No iPfB-cell proliferation was detected in follicular remnants for 4 weeks postdexamethasone treatment, and during a subsequent 3-mon th period, there was limited iPfB-cell proliferation that resulted in a partial regeneration of follicles. Ileal PP involution was also asso ciated with a severe B lymphopenia that persisted for over 14 weeks an d was characterized by the survival of primarily isotype-switched and CD5(+) sIgM(+) B-cells in blood. In contrast, the size of jejunal PP f ollicles was reduced following dexamethasone treatment, but intrafolli cular B-cell proliferation was not arrested. Furthermore, within 4 wee ks, the jejunal PP follicles had recovered in size and cellularity and there was no disruption in IgA plasma-cell production. Thus, dexameth asone selectively depleted iPfB-cells and revealed that the ileal and jejunal PPs contain functionally distinct B-cell populations. The part ial regeneration of the iPfB-cell population indicated that either an intrafollicular, corticosteroid-resistant B-stem cell existed or that ileal PP follicles can be repopulated by circulating B-cells. Finally, the association between ileal PP involution and the absence of circul ating, CD5(-) B-cells confirmed that this lymphoid tissue provides an essential environment for conventional sIgM(+) B-cell development.