Km. Toellner et al., IMMUNOGLOBULIN SWITCH TRANSCRIPT PRODUCTION IN-VIVO RELATED TO THE SITE AND TIME OF ANTIGEN-SPECIFIC B-CELL ACTIVATION, The Journal of experimental medicine, 183(5), 1996, pp. 2303-2312
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.