A role for B cell-activating factor of the TNF family in chemically induced autoimmunity.
After exposure to subtoxic doses of heavy metals such as mercury, H-2s mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we observe that HgCl2 administration in susceptible mice results in the elevated production of B cell-activating factor of the TNF family ((BAFF) also known as BLyS, TALL-1, zTNF-4, THANK, and TNSF13B), a B cell growth factor belonging to the TNF family. A transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)-Ig fusion protein (which neutralizes both BAFF and a proliferation-inducing ligand (APRIL), another TNF family member) inhibited Hg-induced autoantibody or serum IgE production. These results are discussed in the context of the inhibitory effect of TACI-Ig on B cell maturation at the transitional stage.
Zheng
Yan
Y
Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19104, USA.
Gallucci
Stefania
S
Gaughan
John P
JP
Gross
Jane A
JA
Monestier
Marc
M
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000139:chemically induced*; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D008627:Mercuric Chloride