Humoral autoimmunity in mice overexpressing B cell surface CD19: vital role for MHC class II.
B6 mice bearing a transgene (Tg) for human CD19 (hCD19) harbor increased numbers of splenic Ig-secreting cells (IgSC), increased serum levels of total Ig and autoantibodies, but decreased numbers of splenic B cells. To assess the influence of MHC class II (MHCII) to this phenotype, MHCII-deficient CD19-Tg mice were generated. Compared to MHCII-sufficient CD19-Tg mice, splenic IgSC numbers and serum Ig and autoantibody levels were markedly diminished, and the decrease in splenic B cell numbers was aggravated. Remarkably, genetic reconstitution of these MHCII-deficient mice with a human DQ8 Tg resulted in a hierarchical restorative pattern. Restoration of splenic B cell numbers was complete; restoration of numbers of splenic IgSC and of serum Ig levels was partial; and restoration of circulating autoantibody levels was virtually non-existent. Thus, MHCII expression has a profound effect on B cells which can be uncoupled from global Ig and autoantibody production in the hCD19-Tg model. This raises the possibility that MHCII affects B cells in a manner that, at least in part, is independent of helper T cell function.
Stohl
William
W
Division of Rheumatology and Immunology, Department of Medicine, University of Southern California Keck School of Medicine, 2001 Zonal Avenue HMR 711, Los Angeles, CA 90033, USA. stohl@usc.edu
Xu
Dong
D
Kim
Kyoung Soo
KS
Tedder
Thomas F
TF
Sato
Shinichi
S
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D018941:Antigens, CD19; D001323:Autoantibodies; D006183:H-2 Antigens; D011994:Recombinant Proteins