Normal B cell homeostasis requires B cell activation factor production by radiation-resistant cells.
The cellular source of B cell activation factor (BAFF) required for peripheral B cell survival/maturation is unknown. To determine the nature of BAFF-producing cells we established and analyzed reciprocal bone marrow (BM) chimeras with wild-type (WT) and BAFF-deficient mice. The results revealed that BAFF production by radiation-resistant stromal cells is completely sufficient to provide a necessary signal for B cell survival/maturation, as BAFF-/- BM cells transferred into lethally irradiated WT mice gave rise to normal numbers of follicular (FO) and marginal zone (MZ) B cell subpopulations. On the other hand, transfer of WT BM into BAFF-/- lethally irradiated mice resulted only in minimal reconstitution of mature FO B cells and no restoration of MZ B cells. Thus, in the absence of BAFF+/+ stromal cells, BAFF production by BM-derived cells, presumably by macrophages, dendritic cells, and/or neutrophils, was not at all sufficient to support normal B cell homeostasis. Interestingly, immunization of both types of chimeras stimulated high levels of antigen-specific antibody secretion, indicating that either stromal cell- or hematopoietic cell-derived BAFF is sufficient for B cell antibody responses.
Gorelik
Leonid
L
Biogen Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Leonid_Gorelik@biogen.com
Gilbride
Kevin
K
Dobles
Max
M
Kalled
Susan L
SL
Zandman
Daniel
D
Scott
Martin L
ML
D000818:Animals; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival; D005434:Flow Cytometry; D006706:Homeostasis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011827:Radiation; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha