Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.
B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.
Schneider
P
P
Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, Epalinges, Switzerland.
Takatsuka
H
H
Wilson
A
A
Mackay
F
F
Tardivel
A
A
Lens
S
S
Cachero
T G
TG
Finke
D
D
Beermann
F
F
Tschopp
J
J
D000818:Animals; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C490176:Tnfrsf17 protein, mouse; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha