THE IGE ANTIBODY SYSTEM - MATURE, PERIPHERAL LYMPHOCYTES-B EXERT REGULATORY INFLUENCES ON THE IGE SYSTEMS OF SELF-RECONSTITUTING, SUBLETHALLY IRRADIATED MICE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 1  (2) , 83-89
Abstract
Previous studies have documented clear biological differences, such as sensitivity to moderate doses of irradiation, between B lymphocytes of the IgE type and B lymphocytes of other Ig isotypes. The present experiments were originally designed to explore such differences further by comparing the abilities of B lymphocytes derived from various IgE responder phenotypes, which differ among various inbred mouse strains, to reconstitute in a positive way the ability of sublethally irradiated recipient mice (of syngeneic or semisyngeneic type) to mount specific immune responses of the IgE antibody class. This was an important question with regard to fully delineating underlying differences in IgE responder phenotypes among different mouse strains, since heretofore most of the emphasis in experimentally defining such differences has focused on differences in T cell function, rather than B cell function. The experimental approach chosen to address this question seemed logical for 2 reasons: it was expected that, following exposure to the dose of irradiation employed (700 rad), individual mice would only slowly repopulate peripheral lymphoid tissues with their own stem cell products, and the expression of IgE responsiveness observed could be expected to reflect the responsiveness of the donor B cell population transferred into such recipients; and since recipient mice were carrier-primed 1 wk prior to irradiation, in order to create a pool of radioresistant carrier-specific helper T cells, it was expected that this amplified pool of helper T cells would hasten the development of antibody production by the transferred donor B cells. This experimental approach failed to answer the initial experimental question being asked, but instead provided reproducible findings which highly suggest that B lymphocytes can perform regulatory functions, in this case largely suppressive, in an isotype-restricted (i.e., IgE) manner on antibody responses of self-reconstituting, sublethally irradiated mice. The experimental approach, designed to provide an excess of carrier-specific, radioresistant helper T cells, provided milieu for the unusually rapid differentiation of precursor B cells from the recipients'' reconstituting hematopoietic systems, which could interact with the residual radioresistant helper T cells to preferentially develop antibody responses of the IgE class. An interesting aspect of the experimental results is that the type of regulatory influence exerted by donor B cells, i.e., suppression or enhancement, appears to be determined by the IgE responder phenotype of both the donors and recipients of such cells. The findings present evidence for isotype-restricted regulation by B cells, in this case the responses of the IgE class, as contrasted with the more classical examples of such regulation mediated by T cells. This now closes the loop of demonstrated B cell regulatory functions, in that such regulatory B cells display all of the phenotypic functions previously delineated for regulatory T cells.