The immune response to phosphorylcholine (PC) is important because in mice it has been shown to confer a high degree of protection against infection by Streptococcus pneumoniae (S.pn.), a pathogen that poses a significant risk to elderly, very young and immunocompromised individuals. Recently, we have shown that the mouse VH1 gene is essential for immune response to PC and PC-mediated protection against infection by S.pn. Furthermore, we have identified IgL chain structural determinants that may explain differences in the relative affinity/avidity of VH1/VL combinations for different PC containing antigens. Continued analysis of these models should provide insight into the complimentary contribution of interactions between VH and VL genes to protective versus ineffective immune responses to common determinants expressed on different pathogens. Based on our observations in PC transgenic mouse models, we propose that dual receptor expression or ?receptor dilution? is a mechanism by which a host can balance the necessity to avoid self reactivity (which may result in holes in the available repertoire) with the evolutionary pressure to provide protection against specific pathogens. Our current observations in wild type, nontransgenic C57BL/6 mice have demonstrated that dual receptor expressing B cells are a part of the normal wild type B cell repertoire. Interestingly, the VH and VK genes expressed by this small population of B cells in wild type C57BL/6 mice have inferred specificities for both autoreactive antigens as well as antigens expressed on pathogens. These observations suggest that coexpression may be a general mechanism for shaping this subpopulation of the B cell repertoire. More recently, we have shown that TdT (terminal deoxynucleotidyl transferase) plays an important role in shaping the immune repertoire. Specifically, we have demonstrated that the generation of the dominant M603id (idiotype) response to immunization with Proteus moraganii is dependent on TdT expression. Subsequently, we have demonstrated that TdT expression affects the size of a population of autoreactive, PtC (phosphatidylcholine)-specific B1 B cells as well as the expressed VH gene repertoire in this population. Continued examination of the contribution these and other components play in shaping the immune repertoire will further expand our understanding of the mechanisms that distinguish between protective, ineffective and detrimental immune responses.
