: The majority of resting B lymphocytes express both membrane IgM and IgD. However, the expression of these receptors are modulated during other developmental stages. During repertoire acquisition immature B-cells express only IgM whereas after B-cell activation IgD expression is rapidly down-regulated. The reason for the conservation of the complex molecular processes that maintain this complicated pattern of dual expression has not been elucidated since either receptor can function in lieu of the other. We wish to continue studies to understand the molecular basis for the modulation of these receptors during development by dissecting the function of cis-regulatory sequences in the intronic region between the mu and deltaexons. These sequences have been implicated in our previous studies to be involved in both the transcriptional and post-transcriptional processing of the deltaexons. These studies will utilize a newly developed reporter assay that should provide more rapid results. The insights obtained from these experiments will be utilized to construct a target vector for mutation of the regulatory sequences in the endogenous locus in a functionally relevant manner. The responses of this mutant to antigenic challenge should indicate possible deleterious effects of eliminating the modulatory changes in IgD expression on both B-cell activation and memory cell generation. Finally, we wish to utilize a previously generated transgenic mouse that carries a passenger IgD molecule in addition to the endogenous receptors to understand the activation requirements of memory cells. In addition, to discover whether the disturbance in normal memory cell generation exhibited by this transgenic mouse can be directly attributed to monomorphic determinants expressed only by IgD we wish to insert the coding regions for delta cDNA downstream of a heterologous promoter so this transgenic IgD is only expressed after B-cell activation. These studies should provide further insight into the longstanding enigma of dual receptor expression on B lymphocytes.
| Yuan, D; Goldings, E A (1988) Transient expression of pentameric IgM on the surface of NZB B cells. Mol Immunol 25:323-8 |
