The Sm snRNPs play a central role in the processing of pre-mRNA. Anti-Sm antibodies, the diagnostic hallmark of systemic lupus erythematosus, target the B/B and D polypeptides of these snRNPs. We have used patient autoantibodies to clone a cDNA from a human fibroblast cDNA library that encodes the full length of a polypeptide identical with, or closely related to, polypeptide B. This cDNA is comprised of 1139 bases and contains an open reading frame of 855 nucleotides that is capable of encoding 285 amino acids. The first 223 amino acids at the NH2 terminus exhibit nearly complete homology with polypeptide N, a newly recognized brain-and heart-specific component of Sm snRNPs. The derived amino acid sequence for B differs from that of the N polypeptide primarily by a 50-amino acid insert 12 residues upstream from the homologous COOH termini of these polypeptides. The structural differences in these cDNAs for B and N may regulate tissue-specific alternative splicing mechanisms for mRNA. In addition, these clones make it possible to map in fine detail the most characteristic autoimmune responses of systemic lupus erythematosus.The Sm group of small nuclear ribonucleoproteins (the U1, U2, U5, and U4/U6 snRNPs) have a central role in the splicing of pre-mRNA (1-3). These particles are also dominant targets for autoimmune responses in systemic lupus erythematosus (SLE) (4,5). For example, previous studies have demonstrated that anti-Sm autoantibodies, which are diagnostic markers for SLE (6), are directed against the B/B and D polypeptides of these particles (7). Similarly, anti-Ul RNP autoantibodies, which occur in SLE and other connective tissue diseases, are directed against the 70-kDa, A, B/B, and C polypeptides of the U1 snRNP (7-10). The other U1 snRNP polypeptides known as E, F, and G are rarely targets for autoimmune responses. These studies have made it clear that the B/B polypeptides are pivotal in the autoimmune responses of SLE.Recent studies have provided some insights into the structure of the B polypeptides and their relationship to the Sm snRNPs. Only a single B polypeptide is apparent in rodent tumor cell lines, whereas human cells contain the B/B doublet described above (11-13). These latter polypeptides are closely related and possibly represent variants of a single protein (14). In studies based on immunoblots, anti-Sm antibodies were noted to recognize a polypeptide in rat brain tissue referred to as N, which appeared slightly larger than polypeptide B' in NaDodSO4 polyacrylamide gels. Subsequent studies showed that N is an Sm snRNP component specific to brain and heart tissue of both humans and rodents (15). It is currently thought that such unique snRNP polypeptides might provide a basis for tissue-specific mRNA splicing mechanisms (15). Other studies have shown that the B7/B polypeptides likely associate with the U-series small RNAs indirectly through binding to the D, E, F, and G polypeptides (16).In the present study we have cloned and sequenced the entire length of the cDNA that enco...