The process of class switching, whereby B cells switch from production of one class of immunoglobulin (Ig) to another, is highly regulated as different classes are expressed in response to different antigens and at different sites in the body. Ig class switching is effected by a DNA recombination event which replaces the Cmu gene with one of the other heavy chain constant region (CH) genes located 3' to the Cmu gene. How the specificity of this event is controlled is unknown. However, it has been shown that IgM+ cells capable of switching to specific antibody classes have the corresponding unrearranged CH genes in an accessible or active chromatic state, as demonstrated by the fact that these specific CH genes are hypomethylated and are transcriptionally active. We propose to continue our studies on the regulation of Ig class switching using the mouse B cell lymphoma, I.29 IgM+ cells cloned from this lymphoma can be induced to switch from expression of IgM to IgA or less frequently to IgE or IgG2a, by treatment with LPS. This cell line will be used to ask questions about how the class specificity is controlled, especially focusing on the unction of transcription from the germline Ig C alpha genes prior to heavy chain switching. We plan to determine how certain T cell lymphokines which regulate switching activate transcription of the germline alpha and epsilon genes. We also propose to begin to identify cDNAs for genes which are induced in B cells in the process of undergoing class switching. We will attempt to select cDNAs that can cause switch recombination in a transfected plasmid.
Showing the most recent 10 out of 68 publications
