Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice.

The immune system of aged individuals often produces antibodies that have lower affinity and are less protective than antibodies from young individuals. Recent studies in mice suggested that antibodies produced by old individuals may be encoded by distinct immunoglobulin (Ig) genes and that the somatic hypermutation process in these individuals is compromised. The present study employed Ighb scid mice reconstituted with normal lymphocytes from young (2-3-mo-old) and aged (20-25-mo-old) donors and immunized with a protein conjugate of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) to determine whether the molecular changes in antibody repertoire reflect senescence in the B cells or whether they are mediated by the aging helper T lymphocytes.

Facultative role of germinal centers and T cells in the somatic diversification of IgVH genes.

The development of memory B cells takes place in germinal centers (GC) of lymphoid follicles where antigen-driven lymphocytes undergo somatic hypermutation and affinity selection, presumably under the influence of helper T cells. However, the mechanisms that drive this complex response are not well understood. We explored the relationship between GC formation and the onset of hypermutation in response to the hapten phosphorylcholine (PC) coupled to antigenic proteins in mice bearing different frequencies of CD4+ T cells.

Repertoire diversity of antibody response to bacterial antigens in aged mice. IV. Study of VH and VL gene utilization in splenic antibody foci by in situ hybridization.

Mouse Abs against a bacterial epitope, the phosphorylcholine (PC) hapten are encoded by the T15 genes VH1(S107) and V kappa 22. It has been shown that PC-specific hybridomas from aged animals often express IgV gene families other than T15. To determine the extent of this age-dependent molecular shift in the anti-PC response, we examined antibody-forming cells (AFC) in individual young (2 to 4 month) and aged (20 to 24 month) mice by an in situ RNA hybridization.

Distinct pathways of B cell differentiation. I. Residual T cells in athymic mice support the development of splenic germinal centers and B cell memory without an induction of antibody.

B cell memory to T cell-dependent Ags develops in the germinal centers (GC). Here we report that thymus-deficient, nu/nu mice immunized with phosphorylcholine coupled to keyhole limpet hemocyanin (EPC-KLH) develop GC in the spleen in the absence of Ab-forming cell (AFC) response. However, the formation of GC on EPC-KLH immunization requires T cells, because 1) CB.

Exogenous interleukin-2 abrogates differences in the proliferative responses to T cell mitogens among inbred strains of mice.

The proliferative response of spleen cells from BALB/c mice to stimulation with a T cell mitogen, concanavalin A (Con A), was two or more times stronger than that of cells from C57BL/10SnSc (B10) mice. In contrast, the cells from B10 mice responded better to B cell mitogen bacterial lipopolysaccharide (LPS). The differences in the proliferative response to Con A stimulation were not associated with the function of macrophages nor did they depend on IL-1.

In vivo and in vitro immunosuppression by boar seminal vesicle fluid fraction.

Boar seminal vesicle fluid inhibits blast transformation of porcine lymphocytes. Boar seminal vesicle fluid was precipitated in 8% ethanol and the dissolved precipitate separated into two peaks upon chromatography on a Sephacryl S-200 column. The inhibitory activity was found predominantly in the second peak.

Effect of monosodium glutamate on cell-mediated immunity.

Cell-mediated immunity was investigated in adult mice and rats treated with monosodium glutamate in their suckling period. Delayed-type hypersensitivity to xenogeneic cells and host-versus-graft reactivity to allogeneic cells were depressed in these mice. Their splenocytes showed reduced mitogen-induced blastogenesis in vitro which was restored by removal of nonadherent to glass spleen cells.

Distinct effects of aminopterin on stimulation of T and B lymphocytes with mitogen.

Aminopterin, a folate antagonist, added to cultures of mouse spleen cells stimulated with T-cell mitogens markedly inhibited, in a dose-dependent manner, [3H]thymidine incorporation into the cells. Contrary to this inhibitory effect aminopterin added at the same concentrations to cell cultures stimulated with B-cell mitogens significantly increased [3H]thymidine incorporation. The inhibitory effect of aminopterin on T-cell activation was completely reversed by adding hypoxanthine to the cultures.

Induction of indomethacin-sensitive suppressor cells by xenogeneic blood transfusion in mice.

The suppressive effect of xenogeneic blood transfusion on T-cell reactivity, observed in both in vivo and in vitro studies, is connected with the development of indomethacin-sensitive suppressor cells.

Failure to detect the presence of pluripotential haemopoietic stem cells in the mouse brain.

Single cell suspensions prepared from adult mouse brains were tested for the presence of pluripotential haemopoietic stem cells (colony-forming units, CFU) by transfer into an irradiated recipient and enumeration of the CFU in the recipient's spleen. In contrast to the findings of others (Bartlett, 1982), we did not detect CFU after injection of brain cell suspensions, although they were detectable after inoculation with bone marrow cells. The number of CFU in recipients after transfer of increasing numbers of brain cells was the same as that detected in the irradiated controls which had not received any transferred cells.

The role of prostaglandin E in the natural suppressor activity of spleen cells from newborn rats.

Spleen cells from newborn to 2-day-old, but not 3-day-old or older, rats suppress the activity of cells from adult animals in xenogeneic local graft-versus-host (GVH) assay. The duration of neonatal suppressor cell activity can be significantly prolonged by treating newborn rats with exogenous prostaglandin E2 (PGE2), and the suppression was completely abolished by administration of PGE inhibitor indomethacin. The results thus demonstrate an involvement of PGE2 in the mechanism of action of neonatal suppressor cells and may explain some discrepancies concerning the nature of natural suppressor cells present in newborn animals.

Suppression of experimental allergic encephalomyelitis in rats by suppressor factor from a permanent T cell line.

An antigen non-specific suppressor factor (SF4) produced by a permanent mouse T cell line inhibits the mitogen- and antigen-induced proliferation of cells in vitro. The suppression of immune response is not restricted by interspecies barrier. Administration of the SF4 factor in vivo had a significant suppressive effect on the induction and manifestation of experimental allergic encephalomyelitis (EAE) in rats.