The role of T cells in the regulation of B cell tolerance.
The study of conventional models of B cell tolerance has suggested that self-tolerance is imposed on B cells at an early stage in their development due to a peculiar sensitivity of immature B cells to tolerance induction. While this concept accounts for some aspects of central B cell tolerance, it is inconsistent with recent reports of tolerance induction in mature splenic B cells from immunoglobulin transgenic mice. We present an alternative model, the hierarchical model (Aust. N. Z. J. Med. 25, 761-767, 1995), in which regulation of naive B cell reactivity is a function of antigen signal strength and availability of T cell help, but is independent of B cell maturation stage. In turn, the development of tolerance or memory in the T cell compartment is dependent on a combination of antigen-MHC recognition by T cells and antigen-nonspecific signalling by antigen-presenting cells. Using a transgenic model of T-B collaboration, we have shown that both immature and mature self-reactive B cells can be rescued and induced to secrete auto-antibody if the B cell determinant is linked to a carrier protein bearing a foreign T cell determinant.
Fazekas de St Groth
B
B
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia. b.fazekas@centenary.usyd.edu.au
Cook
M C
MC
Smith
A L
AL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008211:Lymphocyte Cooperation; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000502:physiology*