The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations

Abstract

Disparate models for the development of peripheral B cells may reflect significant heterogeneity in recirculating long-lived B cells that have not been previously accounted for. We show in this study that the murine recirculating B cell pool contains two distinct, long-lived, posttransitional, follicular B cell populations. Follicular Type I IgMlow B cells require Ag-derived and Btk-dependent signals for their development and make up the majority of cells in the recirculating follicular B cell pool. Follicular type II B cells do not require Btk- or Notch-2-derived signals, make up about a third of the long-lived recirculating B cell pool, and can develop in the absence of Ag. These two follicular populations exhibit differences in basal tyrosine phosphorylation and in BCR-induced proliferation, suggesting that they may represent functionally distinct populations of long-lived recirculating B cells.

Regulation of Follicular B Cell Differentiation by the Related E26 Transformation-Specific Transcription Factors PU.1, Spi-B, and Spi-C

“…To confirm that FO B cells were reduced in frequency in the spleens of PUB mice, splenic B cell subsets were examined by several alternative methods. FO B cells express high levels of cell surface IgD and low levels of cell surface IgM (IgD hi IgM lo ) (34). As shown in Fig.…”

“…Notably, even though overall transitional cell numbers were reduced, in Em-Spi-C + PUB mice the frequency of CD23 + cells was substantially increased, such that the frequency of T1 cells was on average 44%, T2 cells was 24%, and T3 cells was 6% (Fig. 5) (34) from spleens of WT, PUB, and Em-Spi-C + PUB mice. RNA and cDNA were prepared from sorted cells and used as the template for reverse transcription-quantitative PCR (RT-qPCR) to determine the relative steady-state levels of mRNA transcripts.…”

The development of mature B lymphocytes requires the combined function of CD19 and the p110δ subunit of PI3K

“…2 In wild-type mice this long-lived population has been shown to develop independently of antigen and the tyrosine kinase btk, a well-characterized effector of the PI3K pathway. 42 Our data further suggest that this population can develop in the absence of either CD19 or p110δ. By contrast, IgM low /IgD high immature and recirculating B cells for the expression of kappa and lambda light chains (Fig.…”

“…Type I FO B cells may therefore require CD19 and p110δ in addition to relatively strong BCR stimulus and btk for their correct development. 42 Here we have shown an elevated level of RAG gene expression in lymph node B cells that lack both CD19 and p110δ. BCR signals generated in the absence of antigen engagement, in addition -/-CD19 -/-mutant mice were subjected to western blot analysis with antibodies against p100/p52, c-Rel and β-actin.…”

Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells

“…12 The major population of mature B cells, follicular B cells, expresses an intermediate level of Cr2/CD21 that fluctuates according to immunogenic challenge. 13 Research conducted in mouse models has been integral to the current understanding of B-cell development. However, there are important differences in CR2/CD21 between mouse and human (reviewed in Ref.…”