Effects of anti-immunoglobulin antibodies, interleukin-4 and second messenger agonists on B cells from neonatal mice.

Crosslinking of surface Ig receptors on mature B cells with mitogenic anti-Ig antibodies stimulates phosphoinositide breakdown with subsequent activation of protein kinase C (PKC) and elevation of [Ca2+]i leading to B-cell activation. This response can be mimicked using second messenger agonists such as phorbol 12,13-dibutyrate (PDB) plus a Ca2+ ionophore. Furthermore, interleukin-4 (IL-4) synergizes with sub-mitogenic concentrations of anti-Ig (or with PDB) to activate adult B cells. In contrast anti-Ig does not activate neonatal B cells but rather desensitizes or kills them. The nature of the signals involved in these effects on neonatal B cells is poorly understood. Here we have investigated the proliferative responses of small, resting B cells from 1-, 4-, 8-, and 12-week-old mice stimulated with combinations of anti-Ig, PDB, ionomycin and IL-4. We find that B cells from 8- and 12-week-old mice show an adult pattern of reactivity. B cells from 4-week-old mice respond to high doses of anti-Ig, anti-Ig + IL-4 and also to PDB + ionomycin + IL-4, but not to PDB + ionomycin alone. Neonatal (1-week-old) B cells respond only to the combination of PDB, ionomycin and IL-4. Most strikingly, pre-incubation of neonatal cells with anti-Ig completely abrogates this response, whilst IL-4 renders them refractory to such anti-Ig mediated inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)