Tolerogenicity of resting and activated B cells (original) (raw)
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Journal of Experimental Medicine, 1976
The relative susceptibility of neonatal and adult murine splenocytes to induction of B-cell tolerance was studied in vitro. Adult cells required approximately 1,000-fold more trinitrophenyl-human gamma globulin to be rendered tolerant than did cells from 9- to 12-day-old neonates. The potential effects of suppressor T cells were excluded by pretreating the cultured B cells with anti-Thy-1 and C' and the helper T cells with anti-Ly-2.2 and C'. The possible role of cell surface immunoglobulin isotypes in contributing to this observed difference is discussed.
The Journal of Immunology
In this study, we have investigated the ability of splenic B cells to act as antigen-presenting cells. Previous data had established that lipopolysaccharide (LPS)-activated B cells were effective antigen-presenting cells; however, the relative capacity of resting B cells to carry out this function remains controversial. Splenic B cells from naive BALB/c mice were depleted of macrophages, dendritic cells, and T cells, and were fractionated on the basis of cell density by using Percoll gradient centrifugation. Fractions were collected from the 50/60, 60/65, and 65/72% interfaces and from greater than 72% (pellet). Cytofluorograph analysis of the fractionated B cells showed that the two lower density fractions (50/60 and 60/65) contained a number of cells which, by cell size determination, appeared to be activated B cells, whereas the two higher density fractions (65/72 and greater than 72) appeared to contain predominantly small resting B cells contaminated by many fewer activated B c...
Ontogeny of susceptibility of mouse splenic B cells to tolerance induction in vitro by TNP‐D‐GL
European Journal of Immunology, 1979
The susceptibility of mouse spleen cells to hapten‐specific tolerance induction of a primary in vitro thymus‐independent antibody response was examined. Both the induction of tolerance by 2,4,6‐trinitrophenyl‐D‐glutamic acid‐D‐lysine (TNP96D‐GL) and of antibody formation (elicited by TNP‐Brucella abortus) in neonatal spleen cell cultures were unaffected by anti‐Thy‐1.2 plus complement treatment. Spleen cells from neonatal mice were only slightly more sensitive to TNP96D‐GL tolerance induction than were cells from adult mice. The difference in susceptibility to tolerance induction was not nearly as great as that predicted by “clonal abortion”‐type theories of B cell tolerogenesis.
Journal of immunology (Baltimore, Md. : 1950), 1998
High titers of Ag-specific human IgG were consistently achieved in SCID mice reconstituted with human splenocytes that had been primed with Ag in vitro and then boosted with Ag after engraftment into SCID mice. Specific human IgG titers in the hu-SPL-SCID mice reached approximately 1:4 x 10(5) when the mice were immunized with a neo-antigen, whereas titers reached 1:2 x 10(6) when recall responses were induced. Booster immunizations with Ag 21 days after the initial in vivo boost further enhanced this response, and specific human IgG titers of 1:17 x 10(6) were achieved. This represented an essentially monospecific IgG population. These responses were CD4+ T cell dependent. In addition, affinity maturation of the human Ab responses was observed. Spleens of hu-SPL-SCID mice with Ag-specific titers < or = 1:1 x 10(6) were often significantly enlarged and often displayed visible tumors. Fourteen of sixteen B cell tumors removed from spleens of five such hu-SPL-SCID mice, produced Ab...
European Journal of Immunology, 1988
A noncognate interaction with anti-receptor antibodyactivated helper T cells induces small resting murine B cells to proliferate and to secrete antibody* Culture of small resting allogeneic B cells (of an irrelevant haplotype) with two clones of T helper (Th) cells that were activated by the F23.1 anti-T cell receptor antibody led to the activation of B cells to proliferate and to secrete antibody. Th cell supernatants by themselves had no effect on resting B cells (even in the presence of intact €23.1 antibody), but could induce antibody secretion by anti-Ig-preactivated B cells. Both F23.1' clones (E9.D4 and 4.35F2) and one F23.1-clone (D2.2) could synergize with supernatants from activated E9.D4 T cells to induce B cell activation. F(ab'), fragments of F23.1 induced E9.D4 to activate B cells as efficiently as intact F23.1, and B cell populations that had been incubated with F23.1 were not activated when cultured with E9.D4, although T cells recognized cell-presented F23.1 and were weakly activated. Reduction of the density of F23.1 adsorbed to plastic resulted in weak T cell activation, and these T cells did not induce B cell responses. Haptenated B cell populations, although recognized by E9.D4, were not activated. Separation of T and B cells by a 0.4-pm membrane prevented T-dependent B cell activation, although Th cell-derived B cell-activating lymphokines would be assayed across these membranes. These results suggest a polyclonal noncognate B cell activation that depends on physical contact between B cells and activated T cells. The requirement for a cognate interaction of T h with B cells for the production and delivery of B help can therefore be overcome by activating Th cells with high densities of T cell receptor ligands.
Journal of Experimental Medicine, 1977
During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a "triggering" isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult splenocytes (which are predominantly μ(+)δ(+)[4-6]) and neonatal splenocytes (which bear predominantly IgM [μp(+); 1, 4-6]) to tolerance induction were compared. The results indicate that neonatal splenic B cells responsive to thymus dependent (TD) antigens are exquisitely susceptible to tolerance induction compared with those from adult mice (7-9). However, cells from both adult and neonatal mice were highly susceptible to tolerance induction when thymus independent (TI) antigen was used as immunogen (8). These results suggest that the major precursor for the TD response is a μ(+)δ(+)...
The Effect of Desensitization Protocols on Human Splenic B-Cell Populations In Vivo
American Journal of Transplantation Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2007
rabbit antithymocyte globulin (rATG) all have been suggested to have an effect on antibody producing cells, however, supporting data are lacking. To assess the impact of these agents on splenic B-cell populations in vivo, we retrospectively examined 25 spleens removed from patients treated with these agents as part of desensitization protocols in either ABO incompatible or positive crossmatch living donor kidney transplantation. These were compared to control (CTL) spleens removed for trauma. CTLs and spleens removed at transplant after multiple pretransplant plasmaphereses (PP) plus low-dose IVIG showed similar large numbers of naïve B cells (CD20 + and CD79 + ), plasma cells (CD138 + ) and memory B cells (CD27 + cells). Adding rituximab to this PP/IVIG regimen reduced the number naïve B cells, but had no effect on memory or plasma cells. Combination treatment (PP/IVIG, rituximab and rATG) showed a trend toward the reduction of CD27 + cells, but again plasma cells were unchanged. We conclude that none of these protocols reduces splenic plasma cells in vivo. PP/lowdose IVIG does not alter splenic B cells, but the addition of rituximab decreases mature B cells. Memory B cells may be affected by combination therapy including rATG and requires further study.
transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3e alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3e induced a discrete B220 lo , but not a conventional B220 hi subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220 lo cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220 lo cells were phenotypically similar to the B220 lo AA4.1 1 CD23 2 sIgM lo sIgD 2 developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220 lo cells, mice treated with combined anti-CD3e/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3e can induce an expansion of B220 lo B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response. Fig. 5. Splenic B220 lo cells have the potential being primed to produce alloantibodies. (A) Flow cytometric antibody binding experiments
Splenic B cells and antigen-specific B cells process anti-Ig in a similar manner
Cellular Immunology, 1989
B lymphocytes can process and present antigen to T cells. However, the fate of native antigen after its binding to specific B cells, i.e., the intracellular events involved in the processing and recycling of the antigenic fragments to the cell surface for antigen presentation, are not well understood. In the present study, we demonstrate that murine B cells degrade anti-Ig