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J Sprent

Publications and source records attributed to J Sprent.

At least 163 records · Page 9Linked to original sources
PubMed1985

Capacity of small B cell-enriched populations to stimulate mixed lymphocyte reactions: marked differences between irradiated vs. mitomycin C-treated stimulators.

To investigate whether small B cells can stimulate mixed lymphocyte reactions (MLR), highly purified populations of large vs. small B cell fractions were tested for their capacity to evoke MLR across Mls vs. H-2 barriers. Large B cell fractions stimulated high MLR to Mls and H-2 determinants, irrespective of whether the stimulators were exposed to irradiation or pretreated with mitomycin C. In accord with the findings of others, irradiated small B cell fractions proved to be very poor stimulators of MLR. Significantly, however, mitomycin C-treated small B cell fractions elicited high MLR, particularly to Mls determinants. The finding that small B cell fractions treated with irradiation are poor stimulators of T cells correlates with the known radiosensitivity of B cells. In this respect, the widely held view that small B cells do not have antigen-presenting cell (APC) function rests largely on studies with irradiated B cells. The present finding that T cells respond well to small B cells treated with mitomycin C, however, indicates that small B cell fractions do have APC function. Whether the APC function of small B cells reflects a response to resting B cells per se rather than to cells undergoing activation in vitro, however, remains to be ascertained.

Animals↗
PubMed1985

Physiology of B cells in mice with X-linked immunodeficiency. I. Size, migratory properties, and turnover of the B cell pool.

In terms of certain immune functions and density of surface IgM, B cells from xid mice are often viewed as the equivalent of the immature (Lyb-5-) B cell subset of normal adult mice. In this paper we examine xid B cells with regard to certain physiologic functions, including homing to the lymphoid tissues, recirculation, and turnover. Xid mice were found to possess about one-third of the total number of B cells found in normal mice. This applied irrespective of whether one examined the spleen, lymph nodes, or outputs of B cells in thoracic duct lymph. In terms of migration to spleen, lymph nodes, and Peyer's patches, capacity to recirculate from blood to thoracic duct lymph, and turnover, xid B cells proved to be indistinguishable from normal spleen or thoracic duct B cells. Within these parameters, most xid B cells closely resemble the normal mature long-lived population of B cells residing in the recirculating pool of normal mice. Because xid B cells are functionally quite different from normal mature B cells, it seems reasonable to view xid B cells as an abnormal population not represented in normal mice.

Animals↗
PubMed1985

Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences.

Information was sought on the phenotype of lymphoid cells causing lethal graft-vs-host disease (GVHD) in irradiated mice expressing whole or partial H-2 differences. In all strain combinations tested, pretreating donor lymph node (LN) cells with anti-Thy-1 monoclonal antibodies (MAb) plus complement (C) abolished mortality. With GVHD directed to class I H-2 differences, pretreating LN cells with anti-Lyt-2 MAb prevented mortality, whereas MAb specific for Ly-1 or L3T4 cell surface determinants caused severe mortality. These data imply that lethal GVHD directed to class I H-2 differences is mediated by L3T4-, Lyt-2+ cells; this subset of T cells was shown previously to control GVHD directed to multiple minor histocompatibility antigens, i.e., antigens seen in the context of self-class I molecules. With whole H-2 differences, GVHD appeared to be controlled largely but not exclusively by L3T4+, Lyt-2-T cells. This T cell subset was also the predominant cause of GVHD directed to class II differences. With class II incompatibilities, depleting donor cells of L3T4+ T cells, either by pretreatment with anti-L3T4 MAb + C or by fluorescence activated cell sorter selection, greatly reduced but did not completely abolish GVHD. These data might imply that L3T4-, Lyt-2+ cells have some capacity to elicit anti-class II GVHD. A more likely possibility, however, is that the residual GVHD to class II differences observed with Lyt-2+-enriched cells reflected minor contamination with L3T4+ cells.

Animals↗
PubMed1984

Physiology of B cells in mice with X-linked immunodeficiency (xid). III. Disappearance of xid B cells in double bone marrow chimeras.

Evidence is presented that B cells from mice with X-linked immunodeficiency (xid) differentiate at a slower rate than normal B cells. This conclusion stems from studies in which (B6 X CBA/J)F1 mice were heavily irradiated (1,000 rads) and reconstituted with a mixture of T-depleted marrow cells taken from (a) nondefective B6 mice (H-2b) and (b) xid CBA/N or nondefective CBA/Ca mice (both H-2k). With transfer of CBA/Ca plus B6 marrow cells, the irradiated recipients become repopulated with B cells derived from both parental marrow sources; except for an early imbalance (probably reflecting Hh resistance), the degree of chimerism remained relatively stable over a period of more than 6 months. Very different results occurred with transfer of a mixture of xid CBA/N and normal B6 marrow. Within the first 2 months after marrow reconstitution, a low but significant proportion of the B cells in both spleen and lymph nodes were of CBA/N origin. Thereafter the proportion of these cells fell progressively, and by 6-9 months virtually all of the B cells were of B6 origin. This gradual decline in CBA/N-derived cells did not apply to other cell types, i.e., T cells or pluripotential stem cells. Analogous results were obtained with transfer of CBA/N vs. CBA/Ca marrow cells into sublethally irradiated (750 rads) (CBA/N X DBA/2)F1 male vs. female mice. For example, CBA/N-marrow derived B cells differentiated effectively and survived for long periods in F1 male mice (xid----xid) but not in F1 female mice (xid----normal). The finding that xid B cells eventually disappear in the presence of normal B cells strengthens the view that xid B cells are an abnormal population not represented in normal mice.

Animals↗
PubMed1984

Negative selection in vivo reveals expression of strong Mls determinants in mice with X-linked immunodeficiency.

Evidence is presented that mice with X-linked immunodeficiency (xid) express strong Mlsa,d determinants, a putative marker of the mature subset of B cells. Although young (3-5 wk) (CBA/N X DBA/2)F1 male (xid+) mice stimulated only very weak mixed lymphocyte reactions (MLR) to Mlsa,d determinants, older mice (greater than 7 wk) regularly elicited conspicuous responses, despite being totally unresponsive to TNP-Ficoll. Expression of Mlsa,d determinants by xid+ mice was also detected by the procedure of negative selection in vivo. Thus BALB/c T cells were totally depleted of Mlsa,d reactivity after blood to lymph recirculation through 10-wk old irradiated xid+ (CBA/N X DBA/2)1 male mice. Significantly, a marked (90%) reduction in the anti-Mlsa,d response also occurred with T cell filtration through 3-wk xid+ mice, i.e., mice that elicit only minimal primary MLR; filtration through 3-wk xid- normal female mice led to near-complete (99%) negative selection. Collectively these data indicate either, (a) that xid+ mice contain appreciable numbers of cells with at least some of the properties of mature B cells, or (b) that the expression of Mlsa,d determinants is not restricted to mature B cells. In either case, B cells from xid mice cannot be viewed as a simple model for immature normal B cells.

Aging↗
PubMed1984

Physiology of B cells in mice with X-linked immunodeficiency. II. Influence of the thymus and mature T cells on B cell differentiation.

Evidence is presented that the in vivo differentiation of B cells expressing X-linked immunodeficiency (xid) is controlled by mature T cells. Normal (C57BL/6 X CBA/J)F1 mice were thymectomized (ATx), heavily irradiated, and reconstituted with CBA/N (xid) or CBA/Ca (nondefective) marrow. In contrast to sham-operated mice, ATx recipients of xid marrow showed an almost total absence of Ig+ B cells in lymph nodes (LN) and thoracic duct lymph at 2 mo post-reconstitution ; B cells were markedly reduced in the spleen in some mice but only moderately in others. Addition of mature T cells soon after marrow reconstitution substantially abrogated the B cell depletion. In control experiments with nondefective B cells, the number of B cells developing in ATx irradiated recipients of normal (xid-) marrow cells was not detectably lower than in sham-operated recipients. These data imply that a subset of T-dependent B cells is either missing in normal mice or present in only very small numbers.

Animals↗
PubMed1983

Lethal GVHD across minor histocompatibility barriers: nature of the effector cells and role of the H-2 complex.

Transfer of T-cells to heavily irradiated, H-2-compatible mice frequently leads to a high incidence of lethal graft-versus-host disease (GVHD). Lymphoid cells depleted of Thy1+ cells fail to cause GVHD. Studies with a variety of different, H-2-compatible, strain-combinations suggest that minor, histocompatibility antigens (minor HA) are the main targets for eliciting lethal GVHD. Experiments in which T-cells are negatively selected to minor HA by acute blood-to-lymph recirculation through irradiated hosts have indicated that the T-cells eliciting GVHD to minor HA, are H-2-restricted. In H-2-compatible hosts, the donor T-cells recognize the minor HA of the host and become temporarily trapped in the lymphoid tissues for 1-2 days; during this stage of negative selection, the donor T-cells entering the lymph are specifically devoid of cells able to elicit GVHD against the host, minor HA on further transfer. When the selection host is H-2-different with respect to the donor T-cells, by contrast, the T-cells ignore the host, minor HA and negative selection fails to occur. The T-cells recirculate normally and are unimpaired in their capacity to elicit GVHD on further transfer. By the use of various H-2-recombinant mice as selection hosts it has been shown that, as for T-cells exerting cell-mediated lympholysis (CML) to minor HA in vitro, the T-cells which elicit lethal GVHD to minor HA comprise two distinct subsets of H-2-restricted cells. One subset recognizes minor HA in the context of H-2K (or K end) molecules whereas the other is specific for minor HA-plus-H-2D. Curiously, in marked contrast to the findings on CML responses in vitro, no evidence has been found that H-2I-restricted T-cells contribute to GVHD, either as effector cells or as helper cells. Purified populations of Lyt 1-2+ T-cells have potent GVHD activity, whereas Lyt 1+2- cells fail to cause GVHD. Studies with various types of bone-marrow chimeras suggest that in the induction phase, T-cells recognize minor HA only on lymphohematopoietic cells. In the effector phase, by contrast, non-marrow-derived cells appear to be the main targets of attack. Although the pathogenesis of GVHD is poorly understood, the lethal form of the disease probably reflects the penetration of mucosal surfaces by pathogenic organisms, perhaps as the result of direct destruction of epithelial cells by minor HA-specific cytotoxic lymphocytes. Direct support for this notion has yet to be obtained.

Animals↗
PubMed1982

Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers.

Evidence is presented that T cells that produce lethal graft-vs.-host disease (GVHD) to minor histocompatibility antigens (minor HA) comprise discrete subgroups of H-2K- and H-2D-restricted T cells; double negative selection of T cells in irradiated H-2 recombinant mice was used to separate these two subgroups. No evidence could be found that I-restricted T cells contributed to GVHD, either as effector cells or helper cells. The (unprimed) precursor cells for GVHD expressed the Thy-1+, Lyt-1+/-2, Ia- phenotype. Studies in which H-2-semiallogeneic bone marrow chimeras were used as hosts for negative selection suggested that presentation of minor HA to T cells during the induction phase is controlled by marrow-derived cells; indirect evidence was obtained that these latter cells can "process" minor HA presented on H-2 different cells and thereby render the antigens immunogenic. Studies in which minor HA-different, H-2-compatible chimeras were re-irradiated and then injected with donor-vs.-host T cells suggested that the effector phase of lethal GVHD involves contact of antigen on non-marrow-derived cells.

Animals↗
PubMed1982

Role of the H-2 complex in induction of T helper cells in vivo. III. Contribution of the I-E subregion to restriction sites recognized by I-A/E-restricted T cells.

Previous studies on negative selection of T cells to sheep erythrocytes in irradiated mice showed that CBA (I-Ak,I-Ek) (kk) T cells comprise two subgroups of cells restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted subset requires that the donor T cells and the selection host share both I-A (E beta) and I-E (E alpha) gene products; only the I-A-restricted cells undergo selection in B10.A(4R) (kb) mice. This paper demonstrates that negative selection of the I-A/E-restricted subgroup of CBA T cells can occur in F1 hybrids between B10.A(4R) and various Ia.7+ (E alpha+) I-E-incompatible strains; selection does not occur in hybrids between B10.A(4R) and Ia.7- (E alpha-) strains. These data suggest that, despite the fact that E alpha chains display detectable structural allelic variations, these chains are functionally nonpolymorphic. This conclusion applies to E alpha k,d,p,r,j chains. With F1 hybrids between B10.A(4R) and another Ia.7+ strain, B10.PL (H-2u), in contrast, only intermediate selection is observed. This finding is consistent with recent evidence that cell surface expression of E alpha-u-E beta dimers displays strong cis preference. In contrast to E alpha+ CBA T cells, E alpha- B10.A(4R) (kb) T cells undergo complete negative selection in hosts matched only in the I-A (and H-2K) subregion, i.e., B10.BR (kk) mice; no selection occurs in B10 (bb) mice. These data imply that Ia-restricted T cells in E alpha- strains are probably restricted solely by I-A molecules.

Animals↗
PubMed1982

Lyb-8.2: A new B cell antigen defined and characterized with a monoclonal antibody.

A DBA/1 B10.D2-specific monoclonal antibody (CY34) is described which defines a new murine B lymphocyte differentiation antigen designated Lyb-8.2. The ontogeny, strain distribution, and cell-surface density of the antigen were studied by radioimmunoassay and by fluorescence-activated cell sorter (FACS) analysis. Lyb-8.2 appears to be expressed on pre-B cells and on all mature B lymphocytes. Lyb-8.2 molecules immunoprecipitated from surface labeled B10.D2 spleen cells migrated in polyacrylamide gels with an apparent mol. wt. of 95,000-105,000 daltons and were bound by lentil lectin. The expression of Lyb-8.2 is controlled by a locus on chromosome 7 that is closely linked to Gpi-1 and RP-2. Added Lyb-8.2-specific antibody did not measurably impair B lymphocyte function in several in vitro systems studied.

Animals↗
PubMed1981

Inhibition of T cell activation in vivo with mixtures of monoclonal antibodies specific for I-A and I-A/E molecules.

(CBA x B6)F1 (Iak x Iab) T cells were activated to sheep erythrocytes in irradiated F1 mice in the presence of various monoclonal anti-Ia reagents and then tested for their capacity to collaborate with B cells from B10.BR (I-Ak, I-Ek) (kk), B10.A(4R) (kb), and B10 (bb) mice. Anti-I-Ak antibodies blocked the generation of help for B10.A(4R) B cells, but not B10.BR or B10 B cells. An anti-I-Ab antibody blocked help for B10 B cells, but not for B10.BR or B10.A(4R) B cells. An antibody (Y-17) specific for I-Ak/Ek and I-Ab/Ek molecules, but not for I-Ak or I-Ab molecules, failed to impair the generation of help for B10.BR, B10.A (4R), or B10 B cells. In marked contrast to injecting each antibody separately, a mixture of anti-I-Ak and anti-I-Ak,b/Ek (Y-17) antibodies virtually abolished the generation of help for B10.BR B cells. A mixture of anti-I-Ak and anti-I-Ab antibodies effectively blocked help for (4R x B10)F1 B cells, i.e., cells expressing hybrid I-A molecules. These two antibodies only marginally impaired help for (CBA x B6)F1 B cells. To block help for (CBA x B6)F1 B cells required selection in the presence of a cocktail of anti-I-Ak, anti-I-Ab, and anti-I-Ak,b/Ek antibodies. The implications of these findings are discussed.

Animals↗
PubMed1981

Role of the H-2 complex in induction of T helper cells in vivo. II Negative selection of discrete subgroups of T cells restricted by I-A and I-A/E determinants.

Previous studies have shown that negative selection of T cells to sheep erythrocytes (SRC) after adoptive transfer to irradiated mice requires a sharing of H-2 determinants between the donor T cells and the selection hosts. This paper examines which part of the H-2 complex controls selection. The results show that, in the case of T cells of the H-2k haplotype, complete selection occurs with donor host matching limited to the I-A through I-E subregions of the H-2 complex. Selection to SRC was partial in I-A compatible, I-E incompatible hosts, minimal or not detectable in I-A incompatible, I-E compatible hosts, but near-complete in hosts matched at both the I-A and I-E subregions. Consecutive selection in hosts matched solely at (a) the I-A subregion and (b) the I-E subregion led to incomplete selection. From these and other findings it is argued that H-2k T cells comprise a mixture of T cells restricted by I-A and I-A/E hybrid molecules.

Animals↗
PubMed1981

Evidence that strong Mls determinants are nonpolymorphic.

Gene products of the murine Mls locus elicit high primary mixed lymphocyte reactions (MLRs). Although this locus is considered to have four alleles, only two of these alleles, i.e., Mlsa and Mlsd, give strong responses in primary MLRs. This paper presents a series of experiments to show that Mlsa and Mlsd are in fact antigenically indistinguishable. Strong Mls determinants thus appear to be nonpolymorphic.

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