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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.

Original publication

DOI

10.3109/08830189709068172

Type

Journal article

Journal

International reviews of immunology

Publication Date

01/1997

Volume

15

Pages

73 - 99

Addresses

Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia. b.fazekas@centenary.usyd.edu.au

Keywords

B-Lymphocytes, T-Lymphocytes, Animals, Mice, Transgenic, Humans, Mice, Lymphocyte Cooperation, Immune Tolerance