IL-4 treatment of small splenic B cells induces costimulatory molecules B7-1 and B7-2.
IL-4 has been shown to be involved in the early stages of B cell maturation. Changes induced by IL-4 include cell enlargement, increased viability, and increased MHC class II expression. However IL-4 alone does not induce B cell activation as defined by proliferation, lymphokine production, or Ig class switching. In this study, we demonstrate that incubation with IL-4 enhances the ability of small splenic murine B cells, normally poor stimulators of murine Th1 clones, to stimulate lymphokine production and proliferation by Th1 clones. Moreover, small resting B cells induce anergy, whereas IL-4-treated B cells do not. IL-4-treated B cells were found to express both B7 (B7-1) and a second ligand for CTLA4Ig (B7-2). Although IL-4 induces both B7-1 and B7-2, the kinetics of expression of these molecules are different: B7-2 is detected by 6 h, whereas B7-1 is not detectable until 48 h. In addition, only CTLA4Ig fully blocks IL-4 induced costimulatory activity; a mAb to B7-1 does not. Thus, these results suggest that IL-4 may function indirectly as a costimulatory factor by inducing costimulatory molecules on resting B cells. Additionally, these findings support our previous findings that an alternative ligand for CD28 and CTLA4 is important in providing costimulation.
Stack
R M
RM
Committee on Developmental Biology, University of Chicago, IL 60637.
Lenschow
D J
DJ
Gray
G S
GS
Bluestone
J A
JA
Fitch
F W
FW
D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D048429:Cell Size; D002999:Clone Cells / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D008562:Membrane Glycoproteins; D051379:Mice; D008811:Mice, Inbred DBA; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008070:Lipopolysaccharides; D008222:Lymphokines; D008562:Membrane Glycoproteins; D015847:Interleukin-4