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 (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.
Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia 2050.
M C
MC
Cook
H
H
Körner
D S
DS
Riminton
F A
FA
Lemckert
J
J
Hasbold
M
M
Amesbury
P D
PD
Hodgkin
J G
JG
Cyster
J D
JD
Sedgwick
A
A
Basten
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002465:Cell Movement; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013154:Spleen / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha