A novel role for accessory cells in T cell-dependent B cell differentiation.
The monocyte requirement for pokeweed mitogen-induced T cell-dependent B cell activation was reexamined. We report a dichotomy in the requirement for accessory cells in B cell proliferation and differentiation. Adherent cell-depleted human peripheral blood mononuclear cells which contained only 5% monocytes generated sufficient T cell help for optimal B cell proliferation. However, the presence of 10 to 20% monocytes were required during the last 5 days of culture for stimulated B cells to become IgG-secreting cells. Similar numbers of monocytes were also needed for anti-CD3-induced B cell differentiation. Moreover, monocytes alone added to previously activated B cells could support B cell differentiation in the absence of T cells. To determine the role of cytokines in this system, we demonstrated that supernatants of adherent cell-depleted PBMC contained decreased IL-6 activity in comparison with unseparated PBMC, but not IL-1, IL-2, or BCGF. Recombinant IL-6, however, added back either alone or with other cytokines could not replace the effects of intact monocytes on B cell differentiation. Physical interaction between the accessory cells and the responder cells was also required. As a minimum, paraformaldehyde-fixed monocytes, IL-6, and IL-1 were needed to reconstitute maximal IgG secretion. These studies suggest that accessory cells capable of producing IL-1 and IL-6 can have direct effects on the terminal differentiation of stimulated B cells.
Shiba
K
K
Department of Medicine, University of Southern California, School of Medicine, Los Angeles 90033.
Stohl
W
W
Gray
J D
JD
Horwitz
D A
DA
D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002469:Cell Separation; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D009000:Monocytes / Q000276:immunology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D007074:Immunoglobulin G; D011043:Pokeweed Mitogens