Systematic Comparison of Gene Expression between Murine Memory and Naive B Cells Demonstrates That Memory B Cells Have Unique Signaling Capabilities

Abstract

Memory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their naive precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of Agspecific memory and naive cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors. We identified genes with differential expression and confirmed the differential expression of many of these by quantitative RT-PCR and of some of these at the protein level. Our initial analysis revealed differential expression patterns of genes that regulate signaling. Memory B cells have increased expression of genes important in regulating adenosine signaling and in modulating cAMP responses. Furthermore, memory B cells up-regulate receptors that are essential for embryonic stem cell self-renewal. We further demonstrate that one of these, leukemia inhibitory factor receptor, can initiate functional signaling in memory B cells whereas it does not in naive B cells. Thus, memory and naive B cells are intrinsically wired to signal differently from one another and express a functional signaling pathway that is known to maintain stem cells in other lineages.

Resting Human Memory B Cells Are Intrinsically Programmed for Enhanced Survival and Responsiveness to Diverse Stimuli Compared to Naive B Cells

“…Overall, naive and memory B cell subsets had very similar expression patterns (supplemental Figs. 1 and 2), 5 confirming results from other studies (7,9,16). However, the gene expression profiles of PCs differed substantially from those of naive and memory B cells, with more than a thousand genes differentially expressed (supplemental Fig.…”

BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

“…Indeed, activated B cell and plasma cell populations up-regulate TACI and BCMA (but not BR3), both of which can bind APRIL more avidly than BLyS and can promote survival (10,24,25). Similarly, memory B cells have increased TACI and decreased BR3 expression but do not appear to express BCMA (26). Memory B cells share the expression of several receptors involved in regulating the renewal of stem cell populations (26), so ligands for these receptors may replace BLyS as key survival factors.…”

“…Similarly, memory B cells have increased TACI and decreased BR3 expression but do not appear to express BCMA (26). Memory B cells share the expression of several receptors involved in regulating the renewal of stem cell populations (26), so ligands for these receptors may replace BLyS as key survival factors. TLR stimulation is required for activation of human B cells (27) and leads to TACI up-regulation on murine FO and MZ cells (24) (29,30) and supports the notion of heterogeneity among memory B cells (2,31).…”

B cells – ontogenesis and immune memory development

“…Further, increase expression of components of intra-cellular signaling pathways -adenosine receptor 2A and isoforms of protein kinase C (Tomayko et al 2008;Tangye and Tarlinton 2009). Memory B cells up-regulate leukemia inhibitory factor receptors that are essential for embryonic stem cell self-renewal (Tomayako et al 2008).…”