The antigen recognition and the signal transduction components of the B cell antigen receptor are differentially localized following BCR aggregation

In order for humoral immune responses to develop, B cells must be able to bind and internalize antigens. These functions are performed by the B cell antigen receptor (BCR), which is also responsible for initiating and transducing activation signals necessary for B cell proliferation and differentiation. The BCR consists of a surface immunoglobulin (sIg) antigen-binding component and the Igalpha/Igbeta heterodimer, which functions as the signal transduction complex. The association of sIg with the Igalpha/Igbeta heterodimer is believed to be necessary for trafficking the BCR to the plasma membrane. Studies done in the early 1990s examined the requirements for trafficking of the BCR to the membrane, however they did not address what happens to the associated BCR components upon cell surface expression and antigen interaction. I have examined surface expression patterns of individual components of the BCR following anti-Ig and antigen-induced aggregation. Specifically, the localization and expression levels of sIg and the Igbeta component of the Igalpha/Igbeta signaling unit were investigated in order to determine their individual participation in the internalization and signal transduction. Using primary murine B cells, I found that while more than 95% of the sIg is internalized following anti-Ig induced aggregation, 20-30% of Igbeta remains on the surface. This behavior is not specific to mature B cells, as it also takes place with the transitional immature B cells as well as cell lines. Using pharmacological inhibitors of endosomal trafficking I was able to conclude that new surface Igbeta expression make only a small contribution to the overall levels of surface Igbeta expressed. I also demonstrated that MHC class II molecules are not required for the Ig-independent cell surface expression of Igbeta despite previous evidence suggesting an interaction between Igalpha/Igbeta heterodimer and MHC class II. These results indicate that sIg and Igbeta may function independently following the initial stages of signal transduction.