Cloned allospecific human helper T cell lines induce an MHC-restricted proliferative response by resting B cells

D. Goldberg, A. Green, A. B. Gottlieb, M. K. Crow, A. Lewison, S. M. Friedman

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

To analyze helper T (T(h)) cell-induced B cell proliferation in man, we have cloned allospecific T(h) cells, grown them as long-term IL 2-dependent T cell lines (TCL), and analyzed their phenotypic and functional properties. The two TCL described in this report, A-7 and A-57, are both composed exclusively of T3+, T4+, T8- T cells blasts. In proliferative assays, with a panel of x-irradiated allogeneic stimulator cells, A-7 was found to proliferate in response to DR3-bearing cells, whereas A-57 responds to DR2-positive stimulators. Both TCL are capable of providing MHC-restricted polyclonal help for allogeneic B cells, as measured in the reverse hemolytic plaque assay. Of greater interest, x-irradiated A-7 and A-57 cells are capable of inducing a proliferative response by allogeneic B cells that is absolutely MHC restricted at the inductive (T(h)-APC) level. Thus, x-irradiated A-7 cells only trigger proliferation by DR3+ B cells, whereas A-57 cells selectively activate DR2+ B cells. In contrast, after antigen-specific activation, x-irradiated A-7 and A-57 cells can recruit a significant proliferative response by allogeneic B cells bearing 'irrelevant' DR antigens. The possibility that T(h)-induced B cell proliferation may be resticted at the effector (T(h)-B cell) level was addressed by fractionating B cell populations into 'activated' and 'resting' subsets by discontinuous Percoll density gradient centrifugation and further purification by employing a monoclonal antibody directed against an antigen expressed on activated B cells (4F2). These studies demonstrate that activated B cells are readily and nonspecifically recruited to proliferate by activated T(h) cells, whereas optimal proliferative responses by resting B cells require MHC restricted T(h)-B cell interaction.

Original languageEnglish
Pages (from-to)1012-1019
Number of pages8
JournalJournal of Immunology
Volume135
Issue number2
StatePublished - 1985
Externally publishedYes

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