Fas receptor signaling is requisite for B cell differentiation.
The Fas/Fas ligand (FasL) pathway has been largely implicated in the homeostasis of mature cells. However, it is still unclear whether it plays a role at the progenitor level. To address this issue, we created chimeric mice by transferring C57BL/6 bone marrow (BM) cells of the lpr (Fas-FasL+) or gld (Fas+FasL-) genotype into Rag-2-/- hosts of the same genetic background. In this model, the consequences of a deficient Fas/FasL pathway on lymphoid differentiation could be evaluated without endogenous competition. Analysis of the chimerism revealed a differential sensitivity of hematopoietic lineages to the lack of Fas receptor signaling. While donor-derived myelo-monocytic cells were similarly distributed in all chimeric mice, mature B cells were deleted in the BM and the spleen of lpr chimera, leading to the absence of the marginal zone (MZ) as detected by immunohistology. In contrast, B cell hematopoiesis was complete in gld chimera but MZ macrophages undetectable. These defects suggest a direct and determinant dual role of FasL regulation in negative selection of B cells and in maintenance of the MZ.
Pasqualetto
Valérie
V
IINSERM U.591, nstitut Necker, Paris, France.
Vasseur
Florence
F
Zavala
Flora
F
Schneider
Elke
E
Ezine
Sophie
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D053222:Fas Ligand Protein; D005838:Genotype; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor