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M, G, AND A PLAQUE-FORMING CELL RESPONSES IN MOUSE SPLEEN CELL CULTURES BY CLASS-SPECIFIC ANTIBODY TO MOUSE IMMUNOGLOBULINS
The suppressive effects of monospecific goat anti-mouse globulins on primary immunoglobulin class-specific plaque-forming cell responses in mouse spleen cell cultures were investigated. Anti-µ suppressed responses in all immunoglobulin classes, whereas anti- The anti-µ was specific for µ-chain determinants; its activity was dose dependent, but was not mediated by killing cells with surface µ-chain determinants. Free The experiments suggest that anti-µ combines with µ-chain determinants in antigen-specific receptors on the surfaces of antibody-forming cell precursors, prevents effective stimulation by antigen and subsequent antibody production. To explain suppression of responses in all Ig classes by anti-µ, several models were proposed. It is not possible to determine from the data whether stimulation of precursor cells with 1 and anti-2 suppressed the 1 and 2 responses but not M or A responses, and anti-A suppressed only A responses. The mechanism of action of the anti-µ was studied in detail because of its suppression of responses in all immunoglobulin classes.M but not G myeloma proteins in solution effectively competed with µ-bearing cells for the anti-µ. An excess of anti-µ was necessary in the cultures for 48 hr to insure complete suppression of 5-day responses. However, after removal of excess anti-µ at 48 hr, responses could be stimulated by newly added antigen in cultures where incubation was prolonged to 7 days. Anti-µ was most effective when added at the initiation of cultures and had no suppressive effect when added at 48 hr. Excess antigen did not effectively compete with anti-µ for antigen receptors. Precursors of antibody-forming cells were shown to be the cell population where the suppressive activity of anti-µ was mediated.G or A receptors requires concommitant stimulation of separate cells with only M receptors, or whether cells bearing M receptors are precommitted to or differentiate into cells capable of synthesis of other Ig classes, or whether receptors of M and another Ig class are present on some virgin precursors or the second Ig receptor appears after antigenic stimulation.
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