X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect.

Self Cite

C B A / N mice, a m u t a n t subline of the C B A / C a strain, have an X-linked B l y m p h o c y t e -i m m u n e defect. These mice and F1 male progeny derived from C B A / N females fail to produce specific a n t i b o d y after i m m u n i z a t i o n with certain thymicindependent (TI) antigens (1-4). In addition, these mice fail to produce I g M or IgG responses to either the T I or T -d e p e n d e n t derivatives of the hapten phosphorylcholine (PC) (5, 6). Moreover, analysis of surface m e m b r a n e characteristics indicates that B cells derived from i m m u n e defective mice fail to express determinants that are present on a population of B lymphocytes that appears late in ontogeny. These include minor lymphocyte-stimulating determinants (7), Lyb5 (8), and Lyb3 (9). Furthermore, the B cells of C B A / N mice have unusually high amounts of surface I g M (sIgM) and exhibit a low ratio of surface 8:/~ heavy chains when c o m p a r e d with the B cells of normal mice (10, 11). These surface characteristics are similar to those that are exhibited by neonatal B cells (10). T a k e n together, these findings are consistent with the hypothesis that the i m m u n e defect(s) in C B A / N mice arise from a m a t u r a t i o n a l arrest either in the development of C B A / N B cells or of a subpopulation of these B cells.Previous studies, which used a modification of the in vitro splenic focus technique (12), have suggested that susceptibility to in vitro tolerance induction m a y serve as a functional marker for developing (immature) B cells and B-cell m a t u r a t i o n (12-14). This conclusion is based primarily on the following observations. (a) 2,4-dinitrophenyl (DNP)-and PC-reactive splenic B cells are tolerizable only for the first few days after their initial expression in the murine neonate (12, 13). (b) Neonatal bone marrow B cells can be rendered unresponsive to antigen longer in development than neonatal splenic B cells (13,14). (c) Whereas adult splenic B cells are not susceptible to in vitro tolerance induction, 25% of adult bone marrow B cells are tolerizable (13,14).

Section: Resultssupporting

confidence: 87%

“…These mice and F1 male progeny derived from C B A / N females fail to produce specific a n t i b o d y after i m m u n i z a t i o n with certain thymicindependent (TI) antigens (1)(2)(3)(4). In addition, these mice fail to produce I g M or IgG responses to either the T I or T -d e p e n d e n t derivatives of the hapten phosphorylcholine (PC) (5,6).…”

mentioning

confidence: 99%

Susceptibility to in vitro tolerance induction of adult B cells from mice with an X-linked B-cell defect.

Metcalf¹,

Scher²

1980

Self Cite

“…Since the specificity for PC exists in the immune repertoire of mice with the X-linked defect, failure to produce antibodies to PC is probably not a result of a loss of genes coding for V-region specificities. Rather, the B-lymphocyte deficiency should be attributed to a maturational defect, as previously suggested (2,5).…”

Section: Resultsmentioning

confidence: 87%

Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten.

Kaplan¹,

Quintáns²

1979

F1 male mice with the CBA/N X-linked defect that are unable to produce plaque-forming cell responses to phosphorylcholine (PC) provide normal PC-specific helper T-cell activity when compared to F1 female littermates. Inhibition of helper activity with anti-idiotypic antiserum indicates that PC-specific T cells from both NBF1 female and male mice possess predominantly BALB/c myeloma protein HOPC-8 idiotypic determinants. Therefore, the CBA/N defect cannot be explained as a deletion of genes coding for V-region anti-PC specificities. The demonstration of helper activity in NBF1 male mice, which occurs in the absence of anti-PC antibody synthesis, also demonstrates the endogenous origin of the T-cell receptor.

“…6. This experiment is predicated on the finding that (CBA/N x DBA/2)F1 male spleen cells have an X-linked defect that is limited to their B cells and totally precludes any TNP-Ficoll response (28)(29)(30). Such defective F1 male mice have no known T-cell abnormalities including no known difference in suppressor cell function (30) subpopulation of cells, but splenic neonatal suppressor T cells were not analyzed in detail for their surface phenotype because they represent such a small fraction of cells in the spleen (even in neonatally mouse thyrnic virus-infected mice).…”

Section: Size and Distribution Of Mouse Thymic Virus-resistant Supprementioning

confidence: 99%

Ly phenotype and mechanism of action of mouse neonatal suppressor T cells.

Mosier¹,

Mathieson²,

Campbell³

1977

Neonatal suppressor T cells were isolated from the thymuses of 10- to 14-day old BDF mice infected at birth with mouse thymic virus. Such cells were enriched for suppressive activity directed against antibody formation by adult B cells and represented a relatively homogenous population of outer cortical cells. Their surface antigen phenotype was found to be: Ly 1+, Ly 2+, TL+, Thy 1+, and H-2+. The cells were larger and contained more DNA than thymocytes from age-matched controls. These findings identify neonatal suppressor T cells as a unique subpopulation separate from most inducible suppressor cells in the adult mouse. The mechanism of action of neonatal suppressor T cells seems to be a reduction in the number of B cells initially triggered by antigen.