Article

Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation

Institute of Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
The Journal of Immunology (Impact Factor: 5.36). 12/2007; 179(10):6808-19. DOI: 10.4049/jimmunol.179.10.6808
Source: PubMed

ABSTRACT Humoral immunity is characterized by the generation of Ab-secreting plasma cells and memory B cells that can more rapidly generate specific Abs upon Ag exposure than their naive counterparts. To determine the intrinsic differences that distinguish naive and memory B cells and to identify pathways that allow germinal center B cells to differentiate into memory B cells, we compared the transcriptional profiles of highly purified populations of these three cell types along with plasma cells isolated from mice immunized with a T-dependent Ag. The transcriptional profile of memory B cells is similar to that of naive B cells, yet displays several important differences, including increased expression of activation-induced deaminase and several antiapoptotic genes, chemotactic receptors, and costimulatory molecules. Retroviral expression of either Klf2 or Ski, two transcriptional regulators specifically enriched in memory B cells relative to their germinal center precursors, imparted a competitive advantage to Ag receptor and CD40-engaged B cells in vitro. These data suggest that humoral recall responses are more rapid than primary responses due to the expression of a unique transcriptional program by memory B cells that allows them to both be maintained at high frequencies and to detect and rapidly respond to antigenic re-exposure.

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    • "As the ability to generate genome-wide expression profiles became more broadly adopted, a large number of studies focused on key molecules and pathways involved in B and T cell responses. In general, most of these studies: (1) compared two or more closely related cell types such as Th1 versus Th2 cells (Hamalainen et al., 2001; Yang et al., 2005), phenotypically defined naive, effector, memory (Holmes et al., 2005; Kaech et al., 2002; Lee et al., 2004; Willinger et al., 2005), and exhausted versus functional effector and memory T cells (Wherry et al., Immunity 32, February 26, 2010 ª2010 Elsevier Inc. 153 Immunity Perspective 2007), or subpopulations of B cells (Bhattacharya et al., 2007; Ehrhardt et al., 2008; Klein et al., 2003; Vinuesa et al., 2002), (2) examined changes in gene expression in response to some stimuli such as antigen or cytokines (Feske et al., 2001; Hess et al., 2004; Liu et al., 2002), or (3) tracked longitudinal changes in lymphocyte populations during an immune response (Kaech et al., 2002). One common theme that emerged from many of these studies is that they focused on detailed analysis of individual genes identified through transcriptional profiling via differential expression and a fold-change cutoff. "
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