MEMORY CELL GENERATION ABLATED BY SOLUBLE-PROTEIN ANTIGEN BY MEANS OFEFFECTS ON LYMPHOCYTE-T AND LYMPHOCYTE-B COMPARTMENTS

Adult C57BL/6 mice were injected with 100-mu-g of soluble, freshly dea ggregated human serum albumin (HSA) to produce partial immunologic tol erance. Uninjected normal control (N) mice contain only almost-equal-t o 100 B cells in their spleens with the capacity to (i) be activated i n vitro into clonal proliferation by Escherichia coli lipopolysacchari de plus interleukins 2, 4, and 5, (ii) form IgG1 as well as IgM antibo dy, and (iii) display specificity for HSA when only IgG1 is allowed to score in an enzyme-linked immunosorbent assay (ELISA). Such N mice ge nerate almost-equal-to 50,000 clonable anti-HSA IgG1 antibody-forming cell precursors in their spleens after T-dependent immunization with H SA adsorbed onto alum and given with Bordetella pertussis adjuvant. Mi ce preinjected with soluble HSA (TOL) generate far fewer anti-HSA IgG1 antibody-forming cell precursors, termed anti-HSA memory cells. Splen ocytes were transferred from N or TOL mice into lethally irradiated sy ngeneic recipients together with syngeneic bone marrow. Whereas N sple nocytes generated plentiful memory cells within 2 weeks in antigenical ly challenged recipients, TOL splenocytes did not. Work with Ly-5 cong enic mice ruled out memory cell generation from either the host or the bone marrow inoculum within this limited time. N T cells plus TOL B c ells showed consistently lowered memory cell generation. TOL T cells p lus N B cells showed an even greater lowering of adoptive memory cell generation. Thus the lowered response capacity of TOL mice resided in the T- and B-cell compartments. Attempts to show a suppressor componen t within the T-cell population were inconclusive, but a profound defec t in capacity to respond to HSA in vitro was exhibited by the CD4+ T c ells of TOL mice. B lymphocytes were harvested from T-dependently immu nized mice 5 days after challenge, incubated with soluble HSA for 18 h r, and then adoptively transferred together with N T cells. The recent ly activated B cells were not rendered tolerant by this manipulation. The results argue for a major T-cell component in the process whereby soluble protein antigens ablate affinity maturation and memory cell ge neration.