Interferon-gamma downregulates the proliferative response of hapten-specific B cells stimulated by antigen and cytokines.
IFN-gamma plays a role in many aspects of cellular interactions, both positive and negative. Among its functions during the immune response, the antagonistic effects of IFN-gamma and IL-4 are well documented. Observations in our laboratory suggested that IFN-gamma could also interfere with the activation of single, antigen-specific B cells by antigen and other cytokines. Closer examination revealed that IFN-gamma reduced the number of proliferating cell clones in response to antigen and a variety of cytokines, alone or in combination. Cell viability remained at the initial level and the cells were still able to produce Ig, albeit to a lesser extent than in the absence of IFN-gamma. On the other hand, the frequency of IgM secreting clones was not affected, whereas the total amount of secreted IgM was lower in the presence of IFN-gamma, probably due to the reduced cell number and a decrease in Ig production. In addition, proliferation was prevented when B cells were pre-incubated with IFN-gamma and then stimulated by other cytokines. Kinetic studies revealed that INF-gamma had to be present from the onset of culture because delayed addition did not inhibit the proliferation of the B cells. After its initial action, IFN-gamma could be removed without abolishing the negative signal for proliferation. From these results it can be concluded that IFN-gamma transmits a signal that causes B cells to stop proliferating and prevents them from forming large clones.
Vogel
L
L
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Pike
B L
BL
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA
D000941:Antigens; D016207:Cytokines; D006241:Haptens; D007075:Immunoglobulin M; D007371:Interferon-gamma