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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Antibody Formation* / genetics
-
Antigens / immunology*
-
Antigens / metabolism
-
CD40 Antigens / biosynthesis
-
CD40 Antigens / immunology
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology*
-
Cytidine Deaminase / biosynthesis
-
Cytidine Deaminase / immunology
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology
-
Gene Expression Profiling
-
Gene Expression Regulation / immunology*
-
Germinal Center / immunology
-
Germinal Center / metabolism
-
Immunologic Memory* / genetics
-
Inhibitor of Apoptosis Proteins / biosynthesis
-
Inhibitor of Apoptosis Proteins / immunology
-
Kruppel-Like Transcription Factors / biosynthesis
-
Kruppel-Like Transcription Factors / genetics
-
Kruppel-Like Transcription Factors / immunology
-
Male
-
Mice
-
Plasma Cells / immunology*
-
Plasma Cells / metabolism
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / immunology
-
Receptors, Chemokine / biosynthesis
-
Receptors, Chemokine / immunology
-
Retroviridae
-
Transcription, Genetic / immunology
Substances
-
Antigens
-
CD40 Antigens
-
DNA-Binding Proteins
-
Inhibitor of Apoptosis Proteins
-
Klf2 protein, mouse
-
Kruppel-Like Transcription Factors
-
Proto-Oncogene Proteins
-
Receptors, Chemokine
-
Ski protein, mouse
-
AICDA (activation-induced cytidine deaminase)
-
Cytidine Deaminase