T CELL REGULATION OF B CELL ACTIVATION

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Supernatants of activated cloned T helper cells are capable of replacing T cells in the antigen specific and MHC restricted induction of B cell IgG antibody responses. Two distinct and synergizing activities were identified in this supernatant: Interleukin 4 and an antigen-specific and MHC-restricted factor. This latter factor can be affinity purified employing monoclonal antibodies specific for T cell receptor Vbeta8 determinants. Metabolic labeling and immunoprecipitation with anti-Vbeta8 antibody allowed detection in cell-free helper clone supernatants of a disulfide-linked dimer indistinguishable from the T cellsurface alpha-beta heterodimer. Biochemical analysis demonstrated that the cell-free alpha- beta heterodimer is indistinguishable from the cell-derived form. The cell free alpha-beta heterodimer is selectively associated with components of the CD3/T cell receptor complex in a detergent sensitive and apparently lipid membrane dependent state. The supernatants of activated type 2 T helper cell clone are capable of inducing polyclonal proliferation and immunoglobulin (Ig) secretion by heterogenous unprimed B cell populations. Studies employing recombinant lymphokines have demonstrated that IL5 is sufficient to induce these responses. Recombinant IL5 stimulation results in the appearance of a phenotypically novel B cell population which expresses high densities of Pgp-l (CD44) and relatively low densities of B220 (CD45) and Ia. Cell fractionation experiments demonstrate that the B cell subpopulation expressing this novel phenotype mediates nearly all of the proliferative and immunoglobulin secretory activity of the activated B cell populations. In addition, the Pgp-l expressed by these cells is capable of mediating binding to the extracellular matrix material hyaluronic acid, indicating a potential role for Pgp-l in regulating the trafficking of activated B cells in vivo.