The majority of resting B lymphocytes express on their membranes both IgD and IgM. Because these isotypes have the same V region, either receptor can bind antigen with the same sequelae on the cell. Therefore the reason for the conservation of expression of both Ig classes is not clear. However, one distinction between the two is the tightly regulated ontogenetic appearance of IgD vs IgM. Whereas IgM is present on early B cells in the bone marrow during selection against self antigens, IgD is found only on peripheral B cells. Therefore IgD may appear only at the final stage of maturation of a properly selected B cell and serve to mark it for emigration into the periphery. To test this hypothesis, a mouse strain that expresses transgenic delta mRNA prematurely has been generated. Since B cell numbers are not compromised and endogenous Ig continues to be expressed on virtually all of the B cells it will be possible to use this strain to determine if the precocious expression of IgD alters the B cell repertoire. In addition, because of he deletion of the termination region between the mu and delta genes the expression of mu delta mRNA is also severely compromised. This finding implicates an additional cis--regulatory element for the regulation of mu delta mRNA processing and provides the impetus to further investigate this question. Finally, experiments will be continued to explore the molecular mechanism by which the B lymphocyte switches from synthesis of mRNA for membrane IgM to secretory IgM. Based on the hypothesis that some of the controversial data obtained from investigations of this area stems from utilization of B cell tumors as vehicles for analysis, experiments are proposed herein to re-evaluate the system using primary B cells.
| Yuan, D; Goldings, E A (1988) Transient expression of pentameric IgM on the surface of NZB B cells. Mol Immunol 25:323-8 |
