Immune mechanisms leading to abnormal B cell selection and activation in New Zealand Black mice.
Polyclonal B cell activation is a hallmark of the immune dysregulation in New Zealand Black (NZB) mice. We have previously shown that the splenic B cell activation is associated with increased CD80 expression. Here we show that abnormal expansions of CD80-expressing GC, CD5(+), marginal zone (MZ) precursor and MZ B cells produce this increase. To investigate the role of BCR engagement in the generation and activation of these populations, a non-self-reactive Ig Tg was introduced onto the NZB background. NZB Ig-Tg mice lacked Tg CD5(+) and peanut agglutinin(+) B cells, confirming the role of endogenous Ag in their selection. Although the increased proportion of MZ B cells was retained in NZB Ig-Tg mice, CD80 expression on these cells was reduced as compared to non-Tg NZB mice, suggesting a role for BCR engagement with endogenous Ag in their activation. Examination of CD40L-knockout NZB mice showed no difference in the abnormal activation or selection of the B cell populations, with the exception of GC cells, as compared to wild-type NZB mice. Thus, polyclonal B cell activation in NZB mice does not require CD40 engagement, but results, in part, from dysregulated BCR-specific mechanisms.
Department of Immunology, University of Toronto, Toronto, Canada.
Valerie
V
Roy
Gabriel
G
Bonventi
Yongchun
Y
Cai
Ralph
R
Macleod
Joan E
JE
Wither
D000375:Aging / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D023201:CD40 Ligand / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008814:Mice, Inbred NZB; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand