IMMUNOGLOBULIN SWITCH TRANSCRIPT PRODUCTION IN-VIVO RELATED TO THE SITE AND TIME OF ANTIGEN-SPECIFIC B-CELL ACTIVATION

Immunoglobulin (Ig) class switch recombination is associated with the production and splicing of germline IgC(H) messenger RNA transcripts. Levels of gamma 1 transcripts in mouse spleen sections were assessed b y semiquantitative analysis of reverse transcriptase polymerase chain reaction (PCR) products during primary and secondary antibody response s to chicken gamma globulin (CGG). This was con-elated with the appear ance of CGG-specific B cells and their growth and differentiation to p lasma cells. After primary immunization with CGG, gamma 1 switch trans cripts appeared after 4 d, peaked at a median of six times starting le vels between 10 and 18 d after immunization, and returned to backgroun d levels before secondary immunization at 5 wk. By contrast, after sec ondary challenge with CGG, a sevenfold increase in transcripts occurs during the first d. The level again doubles by day 3, when it is six t imes 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 s econdary immunization, antigen-specific memory B cells appeared in the outer T zone and by 24 h entered S phase, presumably as a result of c ognate interaction with primed T cells. Over the next few hours, they migrated to the edge of the red pulp, where they grew exponentially un til the fourth day, when they synchronously differentiated to become p lasma 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 tran scripts after day 3 indicates that switching also occurs in germinal c enters, but in a relatively small proportion of their B cells. The imp ressive 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, w hich is associated with cognate T cell-B cell interaction in the T zon e, has a major impact on the class and subclasses of Ig produced durin g the response.