Immune mechanisms leading to abnormal B cell selection and activation in New Zealand Black mice

✍ Scribed by Valerie Roy; Gabriel Bonventi; Yongchun Cai; Ralph MacLeod; Joan E. Wither

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 450 KB
• Volume: 37
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200737334

✦ Synopsis

Abstract

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.