REGULATION OF RESTING AND CYCLING HUMAN B-LYMPHOCYTES VIA SURFACE IGM AND THE ACCESSORY MOLECULES INTERLEUKIN-4, CD23 AND CD40

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  • 1 December 1989
    • journal article
    • research article
    • Vol. 68  (4) , 526-531
Abstract
Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-.mu. chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-.mu. only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-.mu. not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The ''background'' stimulation obtained when using a high concentration of immobilized anti-.mu. was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-.mu. needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-.mu. were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4 promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-.mu. in the two populations.