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T Cell Regulation of Specific B Cell Responses¹

From the Sidney Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

Abstract

The role of T cells in the generation of specific antibodies to antigens under Ir gene control was investigated in strain 2 guinea pigs. The specificity of anti-,Dnp-Lys₉ antibody was studied in guinea pigs with intact immune responses and in strain 2 guinea pigs deprived of T cells by adult thymectomy, lethal irradiation, and reconstitution with syngeneic bone marrow cells. Conventional strain 2 guinea pigs developed both T cell responses and highly specific anti-,Dnp-Lys₉ antibody. In contrast, strain 2 "B" guinea pigs failed to develop delayed hypersensitivity and in vitro T cell responses. Nevertheless, these "B" guinea pigs could produce anti-Dnp antibody of restricted heterogeneity and in quantities comparable to those produced by the conventional strain 2 guinea pigs. It was shown that anti-,Dnp-Lys₉ antibody produced in strain 2 "B" guinea pigs lacking specific T cell responses could not distinguish ,Dnp-Lys₉ from dinitrophenol. Similar antibodies are produced in strain 13 guinea pigs that are poly-L-lysine, Ir gene negative. Reconstitution of strain 2 "B" guinea pigs with normal T cells enabled them to develop both cell-mediated immune responses and antibody of highly discriminatory power. These findings support the notion that in the absence of specific T cells, comparably specific B cell antibody responses cannot be generated, and perhaps more importantly, that specific T cells are required to facilitate the amplification of unique B cell clones.

Footnotes

¹ This work was supported in part by Grants CA 19589 and AI-12069 from the National Institutes of Health and from CAPES—Brazil.

² Present address: Instituto de Microbiologia da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.