Control of the IL-2 responsiveness of B lymphocytes by IL-2 and IL-4.
A two-step culture system was used to analyze the parameters involved in the acquisition of IL-2 responsiveness by murine B cells. In the first culture, unstimulated, or resting, B cells prepared from spleen of naive animals were challenged during 48 h with IL-2, IL-4, anti-mu, anti-mu+IL-2, anti-mu+IL4, or anti-mu+IL-2 + IL-4. In a second culture, IL-2 responsiveness was followed by measuring either the cell proliferation or the Ig production. It was found that only B cells stimulated by anti-mu+IL-2 were able to respond. The expression of three chains of the IL-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) was studied by FACS. IL-2R beta and IL-2R gamma were found to be expressed constitutively on resting B cells. IL-2R alpha was induced by anti-mu and anti-mu+IL-2 treatment. Although B cells treated by anti-mu alone are not able to respond to IL-2, they do express an IL-2 binding capacity comparable with B cells treated by anti-mu+IL-2. This paradoxical result suggests that IL-2 has a direct influence on the acquisition of the IL-2 responsiveness. IL-4 exerts a negative effect on the IL-2 response. At the molecular level, IL-4 was found to reduce selectively the IL-2R beta expression at the B cell surface. This effect was confirmed by Northern blot analysis. Maximum expression of the IL-2R beta mRNA is obtained after anti-mu+IL-2 treatment. In the presence of IL-4, expression of the IL-2R beta mRNA is greatly reduced.
Moreau
J L
JL
Unit for Cellular Immunogenetics, Pasteur Institute, Paris, France.
Chastagner
P
P
Tanaka
T
T
Miyasaka
M
M
Kondo
M
M
Sugamura
K
K
Thèze
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis
D007136:Immunoglobulins; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4