Allelic exclusion is the process by which antibody-producing cells (B cells) shut down or exclude from expression one of their two antibody genes after they have started expressing the first. This selectivity is critical to an effective immune response, since it allows each clone of B cells to respond to one particular antigen. The mechanism for this feedback inhibition was not clear, although it had been shown previously in transgenic mouse studies that an activated immunoglobulin transgene could allelically exclude the endogenous genes in most transgenic B cells. Immunoglobulin heavy chain genes encode two mRNAs, one for secreted and one for membrane-bound antibody, and more recently it had been shown that a transgene producing only the secreted form does not mediate allelic exclusion. The work reported here completes the circle, by showing that a transgene that produces only the membrane-bound immunoglobulin is sufficient to cause allelic exclusion, and that this exclusion is tighter than that observed with the transgene making both membrane-bound and secreted forms.
