Abstract
The developmental biology of sheep ileal and jejunal Peyer’s patches (PP) was investigated using corticosteroids to deplete immature B lymphocytes. During a 7-day treatment with dexamethasone, ileal PP follicular (iPf)B-cell proliferation was arrested and most iPfB-cells died. This 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-month period, there was limited iPfB-cell proliferation that resulted in a partial regeneration of follicles. Ileal PP involution was also associated with a severe B lymphopenia that persisted for over 14 weeks and was characterized by the survival of primarily isotype-switched and CD5+ sIgM+ B-cells in blood. In contrast, the size of jejunal PP follicles was reduced following dexamethasone treatment, but intrafollicular B-cell proliferation was not arrested. Furthermore, within 4 weeks, the jejunal PP follicles had recovered in size and cellularity and there was no disruption in IgA plasma-cell production. Thus, dexamethasone selectively depleted iPfB-cells and revealed that the ileal and jejunal PPs contain functionally distinct B-cell populations. The partial 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 circulating, CD5- B-cells confirmed that this lymphoid tissue provides an essential environment for conventional sIgM+ B-cell development.
Highlights
Investigations in rodents have established the concept that after birth, the bone marrow functions as the primary site of B-cell generation (Claman et al, 1966; Mitchell and Miller, 1968; Osmond, 1980), and investigations in both rodents and rabbits revealed that the Peyer’s patches (PPs) function as a secondary, antigen-dependent lymphoid tissue that plays a major role in mucosal immunity (Pollard and Sharon, 1970; Craig and Cebra, 1971; Husband and Gowans, 1978)
Cell suspensions were prepared from lymphoid follicles of the PP and other tissues as described previously (Griebel and Ferrari, 1995; Griebel et al, 1994)
To quantitate lymphocyte subpopulations in blood, the total number of blood mononuclear cells/ml blood was multiplied by the percent mononuclear cells labeled by the appropriate mAb and detected with flow cytometric analyses
Summary
Investigations in rodents have established the concept that after birth, the bone marrow functions as the primary site of B-cell generation (Claman et al, 1966; Mitchell and Miller, 1968; Osmond, 1980), and investigations in both rodents and rabbits revealed that the Peyer’s patches (PPs) function as a secondary, antigen-dependent lymphoid tissue that plays a major role in mucosal immunity (Pollard and Sharon, 1970; Craig and Cebra, 1971; Husband and Gowans, 1978) Consistent with this hypothesis, lymphoid follicles in the PPs develop postnatally in these species PPs may function as a site of both antigen-dependent and antigen-independent B-cell development
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