B-1 cells are deficient in Lck: defective B cell receptor signal transduction in B-1 cells occurs in the absence of elevated Lck expression.
B-1 cells constitute a unique B cell subset that is primarily responsible for producing nonimmune Ig. This natural Ig acts as a principal line of defense against infection. A key feature of B-1 cells is the failure of BCR-triggered signal transduction. Recently, defective BCR signaling in B-1 cells has been attributed to elevated expression of the canonical T cell src kinase, Lck. In the present study, we re-examined Lck expression in normal B-1 cells. We found that B-1 cells expressed less Lck at both the protein and RNA levels than did B-2 cells. The same B-1 cells manifested defective BCR-mediated induction of IKKbeta phosphorylation, IkappaBalpha degradation, and intracellular Ca(2+) mobilization. Thus, the failure of BCR signaling in B-1 cells does not relate to subset-specific elevation of Lck.
Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Rubén
R
Francés
Joseph R
JR
Tumang
Thomas L
TL
Rothstein
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology*; D001483:Base Sequence; D020013:Calcium Signaling; D018076:DNA, Complementary / Q000235:genetics; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
D018076:DNA, Complementary; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D011947:Receptors, Antigen, B-Cell; D000072000:NF-KappaB Inhibitor alpha; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse