Generation and function of natural self-reactive B lymphocytes.
To study the significance of developmentally restricted VH gene expression, and natural self-reactive B lymphocytes, VH81X-mu-heavy chain transgenic mice were constructed and the expression of this gene analysed at different stages of development and in different B-cell subsets. It was found that the majority of B cells expressed the transgenic heavy chain associated with different kappa but not lambda light chains. These B cells were predominantly self reactive and distributed normally to peripheral lymphoid organs. Among the CD23-/IgMhi B cells of transgenic mice there was a population of clonally unrelated relatively self-reactive B cells that expressed identical antigen receptors but did not secrete antibody. Continued administration of antibody of the same specificity during post-natal development reduced the generation of these B cells to very low levels. These studies show that although natural self-reactive B cells are continuously generated as a result of positive selection by self-antigen, their maturation may be blocked at the CD23-/IgMhi stage. Their failure to enter the CD23+ IgMlo B cell pool may prevent them from receiving T-cell help and production of high affinity potentially pathogenic autoreactive IgG antibodies.
Chen
X
X
Department of Microbiology, University of Alabama at Birmingham 35294-3300, USA.
Kearney
J F
JF
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D018956:CD5 Antigens / Q000032:analysis; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D017455:Receptors, IgE / Q000032:analysis
D018956:CD5 Antigens; D007075:Immunoglobulin M; D017455:Receptors, IgE