Activation of human B cells. Comparison of the signal transduced by IL-4 to four different competence signals.
The effects of the cytokine IL-4 on resting and activated human B cells were compared with the effects of known "competence" signals able to drive resting B cells into the cell cycle, including anti-Ig, PMA, anti-CD20, and a recently described competence signal, anti-Bgp95. In proliferation assays, IL-4 was costimulatory with anti-Ig and anti-Bgp95 but not with anti-CD20 or PMA. IL-4 alone triggered increases in expression of class II DR/DQ and CD40, but it did not trigger increases in intracellular free calcium [Ca2+]i in resting B cells or induce resting B cells to leave G0 and enter the G1 phase of the cell cycle. Although IL-4 has some characteristics of competence signals, it was most effective if added to B cells up to 12 h after anti-Ig or anti-Bgp95 rather than before, and thus, in this respect, works more like a progression signal. Like IL-4, all four competence signals for B cells triggered increases in class II and CD40, but only IL-4 consistently induced increases in CD23 surface levels. IL-4 was costimulatory only with anti-Ig and anti-Bgp95, each of which can trigger increases in [Ca2+]i and new protein synthesis of the proto-oncogene c-myc, and can increase attachment of protein kinase C to the plasma membrane. IL-4 was not costimulatory with signals that 1) did not affect [Ca2+]i yet induced c-myc protein synthesis (anti-CD20), 2) only stimulated the translocation of protein kinase C (PMA), or 3) only stimulated increases in [Ca2+]i (calcium ionophore). These results suggest that resting human B cells require at least two intracytoplasmic signals before IL-4 can effectively promote B cell proliferation.
Clark
E A
EA
Department of Microbiology, University of Washington, Seattle 98195.
Shu
G L
GL
Lüscher
B
B
Draves
K E
KE
Banchereau
J
J
Ledbetter
J A
JA
Valentine
M A
MA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D007399:Interphase / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008863:Microspheres; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D015847:Interleukin-4; D002118:Calcium