Transcriptional profiling of antigen-dependent murine B cell differentiation and memory formation.
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.
Bhattacharya
Deepta
D
Institute of Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA 94305, USA. deepta@stanford.edu
Cheah
Ming T
MT
Franco
Christopher B
CB
Hosen
Naoki
N
Pin
Christopher L
CL
Sha
William C
WC
Weissman
Irving L
IL
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D012190:Retroviridae; D014158:Transcription, Genetic / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000941:Antigens; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine; C512653:Ski protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase