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Transcription profiling of mouse naive B cells vs. antigen-specific plasma, germinal center, and memory B cells after immunization with the T-dependent antigen, NP-CGG, in order to generate a transcriptional profile of self-renewal within the hematopoietic system

ABSTRACT: In order to better understand the factors that regulate B cell differentiation upon exposure to antigen, we compares global gene expression profiles from naive B cells with antigen-specific plasma, germinal center, and memory B cells after immunization with the T-dependent antigen, NP-CGG. The memory B cell-enriched transcripts were then compared with memory T cell-enriched and hematopoietic stem cell-enriched transcripts in order to generate a transcriptional profile of self-renewal within the hematopoietic system.

ORGANISM(S): Mus musculus

PROVIDER: E-GEOD-4142 | BioStudies |

REPOSITORIES: biostudies

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Project description:Immunoglobulin (Ig) class switch recombination is associated with the production and splicing of germline IgCH messenger RNA transcripts. Levels of gamma 1 transcripts in mouse spleen sections were assessed by semiquantitative analysis of reverse transcriptase polymerase chain reaction (PCR) products during primary and secondary antibody responses to chicken gamma globulin (CGG). This was correlated with the appearance of CGG-specific B cells and their growth and differentiation to plasma cells. After primary immunization with CGG, gamma 1 switch transcripts appeared after 4 d, peaked at a median of six times starting levels between 10 and 18 d after immunization, and returned to background levels before secondary immunization at 5 wk. By contrast, after secondary challenge with CGG, a sevenfold increase in transcripts occurs during the first d. The level again doubles by day 3, when it is six times that which is seen at the peak of the primary response. After day 4, there was a gradual decline over the next 2-3 wk. Within 12 h of secondary immunization, antigen-specific memory B cells appeared in the outer I zone and by 24 h entered S phase, presumably as a result of cognate interaction with primed T cells. Over the next few hours, they migrated to the edge of the red pulp, where they grew exponentially until the fourth day, when they synchronously differentiated to become plasma cells. The same pattern was seen for the migration, growth, and differentiation of virgin hapten-specific B cells when CGG-primed mice were challenged with hapten protein. The continued production of transcripts after day 3 indicates that switching also occurs in germinal centers, but in a relatively small proportion of their B cells. The impressive early production of switch transcripts during T cell-dependent antibody responses occurs in cells that are about to undergo massive clonal expansion. It is argued that Ig class switching at this time, which is associated with cognate T cell-B cell interaction in the T zone, has a major impact on the class and subclasses of Ig produced during the response.

Dataset Information

Transcription profiling of mouse naive B cells vs. antigen-specific plasma, germinal center, and memory B cells after immunization with the T-dependent antigen, NP-CGG, in order to generate a transcriptional profile of self-renewal within the hematopoietic system

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