Evidence of Functional Lymphocytes

Lymphoid and myeloid cells represent distinct lineages of a common hematopoietic stem cell (1-3). This distinction is dramatically illustrated in the autosomal recessive mouse mutant, scid . t Mice homozygous for the scid mutation (scid mice) are severely deficient in B and T lymphocytes whereas other hematopoietic cell types such as erythrocytes, monocytes, granulocytes, and megakaryocytes (all members of the myeloid series) are present in normal number (4, 5) . Although the scid mutation appears to affect only lymphocyte development (4-10), it is not yet clear what stage of lymphoid differentiation is impaired or arrested . Recent results suggest that the effects of the scid mutation become manifest after the commitment of lymphoid cells to the B and T cell pathways . First, early transcription of unrearranged H chain and TCR loci, which presumably signals the opening of these loci to factors responsible for gene recombination (11-16), is detectable in scid fetal liver and thymus, respectively (Schuler, W., A. Schuler, and M. J. Bosma, unpublished results) . Second, although cells with H chain (or TCR) gene rearrangements cannot be directly demonstrated in freshly harvested lymphoid tissues of adult scid mice (17), early B cell lines with H chain gene rearrangements can be recovered from Abelson murine leukemia virus-transformed scid bone marrow cells (17) and from long-term cultures of scid bone marrow cells (18) . There is also indication of early T cell development as thymic lymphomas with rearranged TCR-'Y and TCR-# alleles spontaneously appear in ^-15% of scid mice (5, 17, 19). It is striking, however, that the majority of rearranged H chain and TCR alleles in transformed scid lymphocytes show abnormal J region deletions. The deletions remove all J-coding exons of a given J region and appear to result from attempted D to J or V to Jjoining ; they vary in size and extend both 5' and 3' of the deleted J regions (17, 19). Evidence of abnormal J-associated deletions has also been reported for rearranged H chain alleles of long-term B cell lines derived from scid bone marrow cells (18) . To explain the abnormal J-associated deletions and how they might account