ALPHA BETA T CELL INDEPENDENT B CELL FUNCTION

Yale University, New Haven CT

Investigators

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Abstract

DESCRIPTION (Adapted from Investigator's abstract): Mice congenitally lacking alpha/beta T-cells frequently display high levels of serum immunoglobulins (Igs). These Igs are of all isotypes which is surprising given the established dependence of IgG, and particularly IgE synthesis, on T-cells. Therefore, a novel pathway of B-cell maturation would appear to be active in alpha/beta T-cell deficient mice. This idea is supported by our finding that such mice also develop germinal centers, anatomical sites associated with T-cell-dependent B-cell maturation. The investigators, therefore, hypothesize that these mice display an heretofore uncharacterized capacity to T-B collaboration between B-cells and non alpha/beta T-cells. Notable among such cells are gamma/delta T-cells, that they have recently shown to "help" B-cells, by demonstrating that mice in which the only T-cells are gamma/delta T-cells, also display germinal centers. Gamma/delta T-cells have not heretofore been ascribed an effector function in B-cell maturation. To test their hypothesis, they plan to characterize B-cell biology in alpha/beta T-cell deficient mice. Interestingly, the antibodies formed in alpha/beta T-cell deficient mice are largely auto-reactive, targeting the same set of antigens as are targeted in human lupus patients. Other recently-derived data demonstrate that alpha/beta T-cell deficient mice indeed develop a lupus-like disease. The investigators, therefore, believe that characterization of the pathway can shed light on immuno-deficiency-associated autoimmune syndromes, such as have been reported in individuals with AIDS, and such as may be operative in one or more cohorts of lupus patients.