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J. Exp. Med.,
Volume 188, Number 8, October 19, 1998 1503-1510
By
From the * Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia 2050;
the Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin Medical Foundation of the University of Sydney, Sydney, NSW, Australia 2050; and the § Department of Microbiology and Immunology, University of California at San Francisco,
San Francisco, California 94143
(LT). 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/LT/ 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/LT/ recipients. This result appeared to account for the defect
in isotype switching observed in intact TNF/LT/ mice because TNF/LT/ 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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