IG HEAVY-CHAIN CLASS SWITCHING IN RAG-DEFICIENT MICE

To investigate potential roles of the RAG-1 and RAG-2 gene products in Ig heavy chain class recombination (CSR), we have generated RAG-1(-/- ) and RAG-2(-/-) mice which contain both a rearranged Ig HC V(D)J gene (referred to as B1-8) inserted into the endogenous Ig heavy chain (HC ) locus in place of the J(H) segments, and a rearranged lambda 1 light chain (LC) transgene (which are referred to as RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda mice respectively), The B1-8 HC gene and lam bda LC genes encode proteins that associate to form a complete Ig mole cule, the expression of which leads to substantial reconstitution of t he peripheral B cell compartments of RAG-1(-/-)B1-8 lambda and RAG-2(- /-)B1-8 lambda mice, Both RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lam bda mice have relatively normal levels of the various IgG isotypes, bu t greatly reduced levels of serum IgM and IgA compared to normal litte rmates, Furthermore, RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda B cells activated in vitro with lipopolysaccharide (LPS) or LPS plus IL -4 responded similarly to control B cells with respect to surface expr ession and secretion of lgG3, IgG1, IgG2b, IgG2a and IgE, but again we re deficient in the secretion of IgM, Together, these findings indicat e that neither RAG-1 nor RAG-2 expression is required for efficient cl ass switching to most HC isotypes in B cells.