Evidence of functional lymphocytes in some (leaky) scid mice.

Abstract

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(11-16), is detectable in scid fetal liver and thymus, respectively (Schuler, W., A. Schuler, and M. J. Bosma, unpublished results) .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

The immunodeficient scid mouse as a model for human lymphatic filariasis.

“…In addition, inflammatory cells were seen accumulating both within lymphatics (E) and in the perilymphatic adipose tissue (F) . Since scid mice lack functional T and B cells (12)(13)(14) and since eosinophilia is dependent on cytokines produced by T cells, two very striking features of this inflammatory infiltrate are the absence of lymphocytes and eosinophils .…”

“…The scid mouse, which lacks functional T and B lymphocytes (12)(13)(14), readily allows the growth and differentiation of infective B. malayi larvae into mature adults, which mate and produce m£ This model should allow the future investigation into the interaction of the murine and human (15,16) immune system with the lymphatic filarial parasite.…”

“…The amount o£ Ig present in the serum of mice was determined by ELISA, as previously described by Bosma et al (12) .…”

MCA Sarcomas Induced in scid Mice are More Immunogenic than MCA Sarcomas Induced in Congenic, Immunocompetent Mice

“…Due to a mutation localized on mouse chromosome 16, presumed to affect an enzyme involved in DNA-splicing, these mice are unable to rearrange the genes coding for the antigen receptors of both T and B lymphocytes [2]. Although some scid mice become 'leaky' with increasing age [3], they do not develop a fully functional immune defence, as the mature T and B cells that do develop are low in numbers and oligoclonal [3]. These scid mice accept engrafted human tumours and other tissues as readily as the classical nude (athymic) mouse, and in some cases even better [4,5].…”

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“…Sometimes, functional antigen receptor rearrangements do occur through 'illegitimate' recombination [5]. A few T and B lymphocyte clones survive and can expand in vivo after exposure to antigens [6]. This phenomenon, that was referred to as 'leakiness' by Bosma et al, is observed in about 15% of young SCID mice, and increases in frequency with age and environmental exposure, especially in mice that are not kept under strict aseptic conditions [6].…”