Feedback regulation of antibody formation by suppressive B cell factor: preferential suppression of high-affinity antibody production by memory B lymphocytes.
Cloned TS4.44 cells, which were hybridized HAT-sensitive 3T3-4E cells with B cells stimulated by immune complexes produce a lymphokine, biochemical and biological characteristics of which are identical with those of conventional suppressive B cell factor (SBF) synthesized by Fc receptor bearing B cells stimulated with immune complexes. This factor is known to suppress B cell responses to antigen/mitogen. The present studies were carried out by using this hybridoma-derived SBF to characterize the large proportion of B cells sensitive to SBF and the small proportion of B cells resistant to it in terms of affinities of antibodies which these cells are able to produce. The treatment of normal spleen cells with SBF resulted in a 50-70% decrease in anti-dinitrophenyl (DNP) antibody production when the cells were transferred into X-ray-irradiated mice along with alum-precipitated dinitrophenyl-conjugated keyhole limpet hemocyanin (DNP-KLH). The affinity of anti-DNP antibody molecules produced in these mice was significantly lower than that of the controls, even if immunization was repeated. The target cells for SBF were B, and not helper T cells which might be involved in the process of affinity maturation. A single treatment of spleen cells in vitro with SBF was sufficient to abrogate the precursors committed to mediate high-affinity anti-DNP antibody responses, since the retreatment with SBF in vitro and transfer into the second irradiated recipients along with antigens of spleen cells of mice to which SBF-treated spleen cells were transferred 3 weeks before resulted in almost the same level of plaque-forming-cell-responses as in mice which received medium-treated.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D004136:Dinitrobenzenes / Q000276:immunology; D005246:Feedback; D005260:Female; D006825:Hybridomas; D007116:Immunization, Passive; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D013154:Spleen / Q000166:cytology; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D004136:Dinitrobenzenes; D013491:Suppressor Factors, Immunologic