GENERATION OF SPLENIC FOLLICULAR STRUCTURE AND B-CELL MOVEMENT IN TUMOR NECROSIS FACTOR-DEFICIENT MICE

Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha). The role of TNF in B cell pos itioning and formation of follicular structure was studied by comparin g the location of newly produced naive recirculating and antigen-stimu lated B cells in TNF-/- and TNF/LT alpha(-/-) mice. By creating radiat ion 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 adoptiv e transfers of mature B cells between wild-type and knockout mice indi cated that normal follicular tropism of recirculating naive B cells oc curs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor-IgG fusion protein administered in vivo failed t o prevent B cell localization to the follicle or the germinal center r eaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF-/- recipients, but not into TNF/LT alp ha(-/-) recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LT alpha(-/-) mice because TN F/LT alpha(-/-) B cells, when stimulated in vitro, switched isotypes n ormally. Thus, TNF is necessary for creating the permissive environmen t for B cell movement and function, but is not itself responsible for these processes.