Allelic exclusion has been the hallmark of immunoglobulin gene expression with gene rearrangement at the DNA level providing the template for the one antibody-one specificity tenet of Burnett's clonal selection theory. Recent findings suggest that this hypothesis may not be totally correct in assuming that only one specificity and that only one antibody is produced from a single B cell. Evidence that receptor editing of immunoglobulin (Ig) light chain genes takes place in the periphery sets the stage for the scenario that with expression of more than one Ig light chain rests the possibility of polyreactivity. Such polyreactive antibodies have been commonly observed in autoimmune diseases as well as in the normal B-cell repertoire suggesting that lymphocytes harboring more than one specificity may be part of the circulating B cell repertoire. Our laboratory was among the first to show that polyreactive antibodies are secreted in mouse plasmacytomas (PC) and that this polyreactivity can be attributed to dual expression of Ig light chain genes from a subset of B cells in the periphery. We have confirmed through micro-dissection of single B cells coupled with RT-PCR amplification of RNA, dual expression of Ig light chain genes occurs within a single PC cell. This population of Dual Light Chain Producing Lymphocytes (DLCPL) may represent an immortalized cell frozen at the precise moment of switch between light chains. As examples of DLCPL have also been found (at low levels of 0.2-3.0%) in normal populations of B cells and including Igk transgene models where 20% of Igl producing B cells are found to co-express Igk , we have proposed an alternative hypothesis that the DLCPL may in fact, represent an immature but normal, component of the B cell population. In order to learn more about the compartmentalization and life-span of the DLCPL, we have undertaken a comprehensive study of tissue- and age-specific expression of the DLCPL using kappa and lambda antibodies in normal BALB/c mice. Based on these preliminary and recent findings, we propose that a certain subset of normal circulating B cells are poly-reactive/multispecific DLCPLs which might represent a putative pre-malignant target in B cell neoplasms. Presumably, upon malignant transformation, these B cells may lose certain specificities associated with the loss of expression of one or more light chain genes. Thus, we propose the polyreactive-double producing B cell may be the preferred therapeutic target of antigen specific B cell tumorigenicity.
| Diaw, L; Siwarski, D; DuBois, W et al. (2000) Double producers of kappa and lambda define a subset of B cells in mouse plasmacytomas. Mol Immunol 37:775-81 |
| Diaw, L; Siwarski, D; Coleman, A et al. (1999) Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas. J Exp Med 190:1405-16 |
