The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 135, 675-697, Copyright © 1972 by The Rockefeller University Press


ARTICLE

IMMUNE RESPONSES IN VITRO : IV. SUPPRESSION OF PRIMARY gammaM, gammaG, AND gammaA PLAQUE-FORMING CELL RESPONSES IN MOUSE SPLEEN CELL CULTURES BY CLASS-SPECIFIC ANTIBODY TO MOUSE IMMUNOGLOBULINS



Carl W. Pierce 1, Susan M. Solliday 1, and Richard Asofsky 1

1 From the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, and the Laboratory of Microbiol Immunity, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20014

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-gamma1 and anti-gamma2 suppressed the gamma1 and gamma2 responses but not gammaM or gammaA responses, and anti-gammaA suppressed only gammaA responses. The mechanism of action of the anti-µ was studied in detail because of its suppression of responses in all immunoglobulin classes.

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 gammaM but not gammaG 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.

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 gammaG or gammaA receptors requires concommitant stimulation of separate cells with only gammaM receptors, or whether cells bearing gammaM receptors are precommitted to or differentiate into cells capable of synthesis of other Ig classes, or whether receptors of gammaM and another Ig class are present on some virgin precursors or the second Ig receptor appears after antigenic stimulation.

Submitted on November 1, 1971


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