Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

Wen L, Pao W, Wong FS, Peng Q, Craft J, Zheng B, Kelsoe G, Dianda L, Owen MJ, Hayday AC
J Exp Med. 1996 183 (5): 2271-82

PMID: 8642336 · PMCID: PMC2192585 · DOI:10.1084/jem.183.5.2271

The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.

MeSH Terms (19)

Animals Autoantibodies Clone Cells Flow Cytometry Germinal Center Humans Immunoglobulin Class Switching Immunoglobulin E Immunoglobulin G Lupus Erythematosus, Systemic Lymphocyte Depletion Mice Mice, Inbred NOD Mice, Inbred Strains Mice, Knockout Mice, SCID Receptors, Antigen, T-Cell, alpha-beta Spleen T-Lymphocytes

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