The Journal of Immunology, Vol 144, Issue 8 2955-2960, Copyright © 1990 by American Association of Immunologists
Soluble factor-independent stimulation of human B cell response by mouse thymoma cells. Cyclosporine A-resistant and -sensitive cell contact signals
XH Zhang, C Hauser and RH Zubler
Department of Medicine, Hopital Cantonal Universitaire, Geneve, Switzerland.
In a Th cell-dependent antibody response, the Th act on B cells partly via
a helper activity that is cell contact-dependent and cyclosporine A
(CsA)-resistant. This activity seems to be required to induce
responsiveness of the B cells toward T cell-derived soluble factors
(cytokines) generally believed to be essential for B cell proliferation as
well as for Ig secretion. In our study, we have investigated a system in
which human B cells are stimulated by mutant EL-4 thymoma cells of mouse
origin. It was found that human B cells proliferate and secrete Ig (either
1) in the presence of EL-4 cells plus human T cell supernatant (T-SUP), or
2) in the presence of EL-4 cells alone which have been induced with PMA or
IL-1. The first situation conformed to the known synergy between
CsA-resistant Th signal and cytokines. However, the B response due to
PMA-induced EL-4 cells was special. The PMA-inducible helper activity was
CsA-sensitive at the same CsA concentration that inhibited IL-2 secretion
of EL-4 cells, but the murine factors in EL-4 supernatant had no effect on
human B cells; the helper effect did not occur across a semipermeable
membrane. Any contribution of soluble factors from contaminating human T
cells was ruled out by adding single human B cells by flow microfluorimetry
to cultures with EL-4 cells and PMA. Such B cells generated clonal IgM,
IgG, and/or IgA responses. CsA, thus, interfered with some cell contact-
mediated signal. However, CsA did not reduce the amount of LFA-1 molecules
on EL-4 cells. In conclusion, EL-4 cells can induce proliferation and
differentiation of human B cells in a soluble factor- independent manner,
via CsA-resistant and CsA-sensitive helper activities. This may represent
an alternative pathway of B cell activation.
