We used somatic cell nuclear transfer (SCNT) to generate a mouse from the nucleus of an IgG1 + ovalbumin-specific B cell. The resulting OBI mice show generally normal B-cell development, with elevated percentages of marginal zone B cells and a reduction in B-1 B cells. Whereas OBI RAG1−/− mice have exclusively IgG1 antiovalbumin in their serum, OBI mice show elevated levels of antiovalbumin of nearly all isotypes 3′ of the γ1 constant region in the IgH locus, indicating that class switch recombination (CSR) occurs in the absence of immunization with ovalbumin. This CSR is associated with the presence of IgM + IgG1 + double producer B cells that represent <1% of total B cells, accumulate in the peritoneal cavity, and account for near-normal levels of serum IgM and IgG3.allelic exclusion | natural antibodies | TN mice B cells exist as a polyclonal pool such that an antibody response may be mounted against any possible pathogen. When a B-cell recognizes its cognate antigen through its B-cell receptor (BCR), the B cell proliferates and differentiates into antibody-secreting plasma cells and a smaller population of memory B cells. Clonal selection theory rests on the idea that a B cell expresses a BCR of a single specificity; harmful consequences could ensue if a B cell activated in the normal course of an immune response also produced a second antibody that reacted with self-antigen. Several mechanisms ensure that a B cell produces only a single specificity BCR, including monoallelic initiation of recombination, restricted access of the RAG proteins, rapid entry into the cell cycle, chromatin remodeling, and subunit pairing constraints (1, 2). Thus, nearly all B cells express a BCR encoded by single alleles at the IgH and Igκ or λ loci. Allelic exclusion, however, is not perfect, and ∼0.01% of B cells express two rearranged IgH genes (3), whereas 1-7% of B cells express two rearranged Igκ genes (4, 5).B-cell development begins in the bone marrow when B-cell progenitors express RAG1/2 and rearrange the Ig heavy chain locus (6). D to J rearrangement occurs first, often on both chromosomes, followed by V to DJ rearrangements. A productive, inframe VDJ results in cell surface expression of the Ig heavy chain paired with VpreB and λ5 surrogate light chains. Pre-BCR signaling induces proliferation and prevents further rearrangements on the other chromosome. After several rounds of cell division, pre-B cells re-express the RAG genes and engage in V to J rearrangement of the Igκ light chain locus. Surface expression of the BCR marks transition to the immature B-cell stage.Once in the periphery, B cells engage a wider array of antigens, including those from food and commensal microbes. Transitional B cells further differentiate into one of three major B-cell populations: long-lived marginal zone (MZ) B cells that reside in the marginal zone sinus of the spleen; follicular B cells that form the B-cell zones of spleen and lymph nodes; and B-1 B cells that reside mainly in the peritoneal cavity and are a major source of natural...