Association of B-1 B Cells with Follicular Dendritic Cells in Spleen

Abstract

Although CD5+ B-1 B cells have been recognized as an infrequent B cell subset in mice for many years, attempts to identify their histologic location in normal mouse spleen have proven difficult due to both their paucity and low level expression of CD5. In this study we have studied VH11/DH/JH gene-targeted mice, VH11t, that develop elevated numbers of CD5+ VH11/Vk9 B cells with an anti-phosphatidylcholine (anti-PtC) autoreactive specificity, allowing B-1 B cell detection by anti-PtC Id-specific Abs in spleen section staining. Using this approach we found that anti-PtC B-1 cells first appear within the white pulp in neonates, expand in association with follicular dendritic cells (FDC), and localize more centrally than other (non-B-1) IgDhigh follicular B cells in adults. Among neonatal B cells, CD5+ B-1 cells in both normal and VH11t mouse spleen and peritoneal cavity express the highest levels of CXCR5, which is important for FDC development. Injection of purified spleen or peritoneal B-1 cells into RAG knockout mice resulted in B-1 cell follicle formation in spleen, inducing FDC development and plasma cell generation. These results indicate that B-1 B cells are the first B cells to express fully mature levels of CXCR5, thereby promoting the development of FDC.

A role for IRF4 in the development of CLL

“…22,23 The Rag2 and common g chain double-deficient mice (Rag2 2/2 g 2/2 ) mice were obtained from Taconic. All mice were maintained under specific pathogen-free conditions.…”

“…21 Analysis of Vh11 knock-in mice confirmed that B cells expressing the Vh11 knock-in allele give rise to B1 cells, whose population is expanded dramatically in the Vh11 knock-in mice. 22 Here, we report that IRF4-deficient mice expressing the Vh11 knock-in allele (IRF4 There is an Inside Blood commentary on this article in this issue.…”

Access to Follicular Dendritic Cells Is a Pivotal Step in Murine Chronic Lymphocytic Leukemia B-cell Activation and Proliferation

“…Although physiologic differences between murine and human B-cell populations exist, prohibiting defi nitive conclusions ( 48 ), similarities are also appreciated that affect structural restriction of the BCRs, the polyreactivity toward autoantigens, expression of CD5, and the presentation as activated antigen-experienced B cells ( 3 , 9 , 49 ). B-1 cells can induce and associate with FDCs in mice; however, traffi cking routes of these cells have not been thoroughly analyzed ( 50 ).…”

Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions

“…Previous studies showed that peritoneal B-1a cells can migrate to the spleen (36,37) and that those present in the pleural cavity can migrate to mediastinal lymph nodes (38). To determine whether the peritoneal B-1a subsets differ in their migratory potential, we adoptively transferred equal numbers of sort-purified subsets i.p.…”