EFFECT OF THE PRESENCE OF TRANSGENIC H-CHAIN AND L-CHAIN GENES ON B-CELL DEVELOPMENT AND ALLELIC EXCLUSION

The expression of various components of the antigen receptor is closel y associated with the developmental progression of B lymphocytes, Far this reason, introduction of rearranged Ig transgenes exerts profound effects on B cell development. In these studies we show that the prese nce of transgenes for both mu and delta H as well as L chains accelera tes the rate of B cell maturation resulting in the appearance of large numbers of IgD-expressing B lymphocytes in vitro that are otherwise u ndetectable, In addition, allelic exclusion, normally exerted very eff ectively by these particular transgenes (carried in the MD-3 strain), was lost in the long-term bone marrow cultures. These findings can be recapitulated in vivo by serial adoptive transfers of bone marrow cell s from the transgenic animals into lethally irradiated recipients. We conclude from these studies that allelic exclusion is not necessarily mediated by any one event but may be a result of the integrated occurr ence of Ig H chain gene rearrangement, accumulation of transcription f actors, along with the ordered progression of B cell differentiation u nder the influence of the appropriate inductive microenvironment, Thes e findings may account for at least some of the observed cases of alle lic inclusion in transgenic animals.