B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the release of soluble CD40.
The expression of CD40 ligand (CD40L) on activated T cells (CD4+ T cell clone MT9) is diminished when the T cells are cultured in the presence of B cells. This effect, observed both with normal tonsil B cells and with the B cell line JY, was detected after 6 h and sustained at least until 18 h of co-culture. Analysis of mRNA showed that CD40L mRNA levels were not modified after 6 h, but were significantly down-regulated after 18 h of co-culture with B cells. Although CD40L expression could not be detected by a CD40-Fc chimera, the molecule was still expressed at the membrane as shown with a polyclonal antiserum against CD40L (anti-TRAP). In addition, T cells activated in the presence of B cells were stained by a polyclonal antiserum against CD40, without the appearance of CD40 mRNA. These results indicated that a soluble form of CD40 (sCD40) bound to the expressed CD40L on T cells. The existence of sCD40 was confirmed by detection of sCD40 in B cell supernatants using a specific enzyme-linked immunosorbent assay. Collectively, these data show that B cells can regulate the expression of CD40L on activated T cells at least by two different mechanisms.
van Kooten
C
C
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Gaillard
C
C
Galizzi
J P
JP
Hermann
P
P
Fossiez
F
F
Banchereau
J
J
Blanchard
D
D
D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*; D013601:T-Lymphocytes / Q000378:metabolism*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand