Normal B cell homeostasis requires B cell activation factor production by radiation-resistant cells

L Gorelik, K Gilbride, M Dobles, SL Kalled… - The Journal of …, 2003 - rupress.org
L Gorelik, K Gilbride, M Dobles, SL Kalled, D Zandman, ML Scott
The Journal of experimental medicine, 2003rupress.org
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 …
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.
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