Autoreactive marginal zone B cells are spontaneously activated but lymph node B cells require T cell help.
In K/BxN mice, arthritis is induced by autoantibodies against glucose-6-phosphate-isomerase (GPI). To investigate B cell tolerance to GPI in nonautoimmune mice, we increased the GPI-reactive B cell frequency using a low affinity anti-GPI H chain transgene. Surprisingly, anti-GPI B cells were not tolerant to this ubiquitously expressed and circulating autoantigen. Instead, they were found in two functionally distinct compartments: an activated population in the splenic marginal zone (MZ) and an antigenically ignorant one in the recirculating follicular/lymph node (LN) pool. This difference in activation was due to increased autoantigen availability in the MZ. Importantly, the LN anti-GPI B cells remained functionally competent and could be induced to secrete autoantibodies in response to cognate T cell help in vitro and in vivo. Therefore, our study of low affinity autoreactive B cells reveals two distinct but potentially concurrent mechanisms for their activation, of which one is T cell dependent and the other is T cell independent.
Mandik-Nayak
Laura
L
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Racz
Jennifer
J
Sleckman
Barry P
BP
Allen
Paul M
PM
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D017634:Self Tolerance / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D001324:Autoantigens; D007136:Immunoglobulins; D005956:Glucose-6-Phosphate Isomerase