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Publication : Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice.

First Author  Cook MC Year  1998
Journal  J Exp Med Volume  188
Issue  8 Pages  1503-10
PubMed ID  9782127 Mgi Jnum  J:50481
Mgi Id  MGI:1306730 Doi  10.1084/jem.188.8.1503
Citation  Cook MC, et al. (1998) Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice. J Exp Med 188(8):1503-10
abstractText  Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin alpha (LTalpha). The role of TNF in B cell positioning and formation of follicular structure was studied by comparing the location of newly produced naive recirculating and antigen-stimulated B cells in TNF-/- and TNF/LTalpha-/- mice. By creating radiation bone marrow chimeras from wild-type and TNF-/- mice, formation of normal splenic B cell follicles was shown to depend on TNF production by radiation-sensitive cells of hemopoietic origin. Reciprocal adoptive transfers of mature B cells between wild-type and knockout mice indicated that normal follicular tropism of recirculating naive B cells occurs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor-IgG fusion protein administered in vivo failed to prevent B cell localization to the follicle or the germinal center reaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF-/- recipients, but not into TNF/LTalpha-/- recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTalpha-/- mice because TNF/LTalpha-/- B cells, when stimulated in vitro, switched isotypes normally. Thus, TNF is necessary for creating the permissive environment for B cell movement and function, but is not itself responsible for these processes.
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