MU switch region deletion is associated with both T cell independent and T cell dependent responses

Abstract

Isotype switching is a process by which immunoglobulin variable gene regions initially proximal to and expressed with the mu constant region gene (C μ) can rearrange downstream to other constant region genes. Thus the same antigen binding site can be expressed with each of the other constant region isotypes and perform the full panoply of effector functions. Although isotype switching is thought to involve highly reiterated ‘switch site’ sequences located 5' to constant region genes, the exact role of these switch sites is unknown. It has been reported that prior to switching, the ‘donor’ switch site 5' of C μ occasionally undergoes deletions, but it is not known whether this is an adventitious event or one which predisposes to or prevents isotype switching. Since T cell independent (TI) immune responses are dominated by IgM while T cell dependent (TD) responses are associated with switching to IgG, we have examined the state of the mu switch site in 51 IgM-producing hybridomas isolated from a variety of TI and TD responses. Although more hybridomas from the TI responses studied exhibited S μ deletions, deletion of S μ also occurred in hybridomas isolated from TD responses. Analysis of a well-characterized clonally related subset of IgM hybridomas also revealed that mu switch region deletion can be associated with the productive allele.