IMMUNOGLOBULIN ISOTYPE PRODUCTION BY CYCLING HUMAN LYMPHOCYTES-B IN RESPONSE TO RECOMBINANT CYTOKINES AND ANTI-IGM

  • 1 March 1990
    • journal article
    • research article
    • Vol. 69  (3) , 342-347
Abstract
Actively cycling populations of purified human tonsilar B lymphocytes were examined for their capacity to secrete IgM, IgA, IgE and IgG of all four subclasses in direct response to recombinant cytokines; in some experiments, monoclonal antibody to IgM (anti-.mu.m) was included in order to explore the influence of antigen receptor ligation on immunoglobulin (Ig) production. Enhanced IgM release was seen on culture of the cycling cells with either interleukin-2 (IL-2), IL-4 or interferonalpha (IFN-.alpha.). IL-2 and IFN-.alpha. also augmented IgA production, whereas IL-4 had no effect on this isotype. IL-4 did, however, encourage the production of the IgG subclasses IgG1, IgG2 and IgG3, while IL-2 augmented IgG1 and IgG3 release and IFN-.alpha. increased IgG levels. IgG4 production, and that of IgE, failed to be perturbed by any of the cytokines assayed. Neither IL-1.alpha., IL-1.beta., IL-5 nor IFN-.gamma. significantly altered the profile of Ig isotype release. When confronted with anti-.mu., cycling B cells demonstrated a marked suppression in IgM production. Suppression could not be overcome by the addition to culture of the normally IgM-promoting IL-4. Concomitant with the reduction in IgM levels, an increase in IgG release was observed. This was comprised of elevations in IgG1 and IgG3. Although not influencing IgA release directly, anti-.mu. was found to promote increased IgA production in co-culture with either IL-2 or IFN-.alpha.. The findings are discussed in the context of recent findings on Ig isotype control in both human and murine systems.