Bone marrow pre-B cells and the clonal anergy theory of immunologic tolerance.
This review begins with a summary of a decade's research from the author's own laboratory which documents the fact that B lymphocytes can receive and store negative, down-regulatory signals from an encounter with antigen, and that the sensitivity to such negative signalling depends critically on maturational status, the most immature B cells being the most susceptible. The review then examines the relationship between these experimentally-induced models of immunologic tolerance, with the pre-B to B cell transition as the critical stage for examination, and the real-life phenomenon of self-tolerance. It makes the point that no repertoire-purging mechanism to ensure self-tolerance can afford to be too effective, for fear of purging too many useful cells, given the number and variability of self-antigens. The review then examines certain dilemmas posed by recent findings in cellular and molecular immunology. These include: 1) the preferential use of particular VH gene families by B cells at different stages of the differentiation process; 2) the apparent frequency of B lymphocytes with the potential for antiself-reactivity in the B cell repertoire; and 3) the existence of a new type of B cell, the Ly-1-positive B cell, with peculiar characteristics. These findings are considered within the particular contexts of pre-B-to-B cell transition and tolerance induction through clonal anergy mechanisms.
Nossal
G J
GJ
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008954:Models, Biological
D001323:Autoantibodies