Cloned allospecific human helper T cell lines induce an MHC-restricted proliferative response by resting B cells.
To analyze helper T (Th) cell-induced B cell proliferation in man, we have cloned allospecific Th 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 (Th-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 Th-induced B cell proliferation may be restricted at the effector (Th-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 Th cells, whereas optimal proliferative responses by resting B cells require MHC restricted Th-B cell interaction.
D
D
Goldberg
A
A
Green
A B
AB
Gottlieb
M K
MK
Crow
A
A
Lewison
S M
SM
Friedman
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002469:Cell Separation; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007399:Interphase; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II