scholarly journals MATURATION OF THE HUMORAL IMMUNE RESPONSE IN MICE

1974 ◽  
Vol 139 (2) ◽  
pp. 249-263 ◽  
Author(s):  
Patricia G. Spear ◽  
Gerald M. Edelman
Keyword(s):  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
Spleen Cells ◽  
Con A ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Humoral Antibodies

In spite of the prenatal appearance of immunoglobulin-bearing lymphocytes and θ-positive lymphocytes in the spleens of Swiss-L mice, these mice are not able to produce detectable levels of humoral antibodies in response to antigen until after 1 wk of age. Adult levels of response are not achieved until 4–8 wk of age. In the presence of bacterial lipopolysaccharides, which can substitute for or enhance T-cell function, the B cells from young Swiss-L mice were found to be indistinguishable in function from adult B cells, both with respect to the numbers of plaque-forming cells (PFC) produced in vitro in response to antigen and with respect to the kinetics of PFC induction. The spleen cells from young Swiss-L mice are significantly less sensitive than adult spleen cells, however, to stimulation by the T cell mitogens, concanavalin A (Con A) and phytohemagglutinin (PHA). Very few Con A-responsive cells could be detected at birth but the numbers increased sharply with age until 3 wk after birth. On the other hand, PHA-responsive cells could not be detected in the spleen until about 3 wk of age. The latter cells were found to respond also to Con A, but at a lower dose (1 µg/ml) than that required for the bulk of the Con A-responsive cells (3 µg/ml). The cells that respond both to PHA and to Con A appear in the spleen at about the time that Swiss-L mice acquire the ability to produce humoral antibodies, and these cells can be depleted from the spleen by the in vivo administration of antithymocyte serum. The development of humoral immune responses in these mice therefore appears to be correlated with the appearance of recirculating T lymphocytes that are responsive both to PHA and to Con A.

Chondroitin sulfate activates B cells in vitro, expands CD138+cells in vivo, and interferes with established humoral immune responses

2014 ◽  
Vol 96 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Hilke Brühl ◽  
Josef Cihak ◽  
Nicole Goebel ◽  
Yvonne Talke ◽  
Kerstin Renner ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Chondroitin Sulfate ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Augmentation of in vitro humoral immune responses in the mouse by an antibody to IgD.

1980 ◽  
Vol 152 (3) ◽  
pp. 493-506 ◽  
Author(s):  
F D Finkelham ◽  
V L Woods ◽  
S B Wilburn ◽  
J J Mond ◽  
K E Stein ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Total Serum ◽  
Adjuvant Effect ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Almost All ◽  
T Cell Help

Heterologous anti-delta-chain antibodies have an adjuvant effect on specific in vivo humoral immune responses to simultaneously, or subsequently, injected antigens in the rat and rhesus monkey. We have used a hybridoma-secreted antibody that binds murine delta-chain of the allotype (4.22aM delta a) to study this phenomenon in the mouse and to investigate the mechanism of this effect. Injection of 4.22aM delta a into BALB/c mice removes almost all surface IgD (sIgD) from splenic B lymphocites. sIgD does not reappear until the serum level of 4.22aM delta a decreased 5-7 d after injection. 4.22aM delta a fails to induce detectable proliferation or to raise total serum Ig levels substantially above control values. However, 4.22aM dalta a injected 24 h before antigen elicits an approximately twofold enhancement of serum IgM and a 3- to 10-fold enhancement of serum IgG anti-trintriphenyl (TNP) antibodies in response to immunization with optimal doses of TNP-Ficoll or TNP-sheep red blood cells (TNP-SRBC). 4.22aM delta a injected 1 wk before or 3 d after TNP-SRBC, however, has no effect on IgG anti-TNP levels. The adjuvant effect of anti-delta-chain antibody was markedly decreased when suboptimal antigen doses were used. Furthermore, even in the case of TNP-Ficoll, a relatively T-independent antigen, the ability of 4.22aM dalta a to enhance the anti-TNP antibody response was T cell dependent. Our data suggest that the binding of anti-delta-chain antibody to cell sIgD may partially activate B lymphocytes and make them more capable of differentiating into antibody-secreting cells when stimulated by antigen-specific T cell help.

scholarly journals The collaborative phenotype of secondary B cells is determined by T lymphocytes during in vivo immunization.

1982 ◽  
Vol 155 (2) ◽  
pp. 574-586 ◽  
Author(s):  
N A Speck ◽  
S K Pierce
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Populations ◽  
Antibody Synthesis ◽  
Humoral Immune ◽  
Igg1 Antibody ◽  
Humoral Immune Responses

Previous studies have demonstrated that the B cells in immune and nonimmune mice manifest different major histocompatibility complex (MHC) collaborative phenotypes with antigen-specific T cells. Immune, or secondary B cells require syngeneic-like MHC recognition by collaborating T cells, and in its absence fail to be stimulated. Primary B cells manifest a much less stringent requisite for MHC recognition by T cells, and under conditions in which secondary B cells fail to be stimulated, primary B cells are stimulated to secrete IgM antibody. Experiments were conducted to determine whether the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference for IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference of IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was found to be dependent on the presence of T cells during in vivo immunization. Thus, the restriction imposed on T cell-B-cell-collaborative interactions in secondary humoral immune responses appears to be the result of T dependent antigen-driven events.

scholarly journals Batf coordinates multiple aspects of B and T cell function required for normal antibody responses

2010 ◽  
Vol 207 (5) ◽  
pp. 933-942 ◽  
Author(s):  
Briana C. Betz ◽  
Kimberly L. Jordan-Williams ◽  
Chuanwu Wang ◽  
Seung Goo Kang ◽  
Juan Liao ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Leucine Zipper ◽  
Cell Function ◽  
Cell Phenotype ◽  
Normal Numbers ◽  
Basic Leucine Zipper ◽  
Robust Immune Response

Batf belongs to the activator protein 1 superfamily of basic leucine zipper transcription factors that includes Fos, Jun, and Atf proteins. Batf is expressed in mouse T and B lymphocytes, although the importance of Batf to the function of these lineages has not been fully investigated. We generated mice (BatfΔZ/ΔZ) in which Batf protein is not produced. BatfΔZ/ΔZ mice contain normal numbers of B cells but show reduced numbers of peripheral CD4+ T cells. Analysis of CD4+ T helper (Th) cell subsets in BatfΔZ/ΔZ mice demonstrated that Batf is required for the development of functional Th type 17 (Th17), Th2, and follicular Th (Tfh) cells. In response to antigen immunization, germinal centers were absent in BatfΔZ/ΔZ mice and the maturation of Ig-secreting B cells was impaired. Although adoptive transfer experiments confirmed that this B cell phenotype can be driven by defects in the BatfΔZ/ΔZ CD4+ T cell compartment, stimulation of BatfΔZ/ΔZ B cells in vitro, or by a T cell–independent antigen in vivo, resulted in proliferation but not class-switch recombination. We conclude that loss of Batf disrupts multiple components of the lymphocyte communication network that are required for a robust immune response.

scholarly journals In vitro analysis of allogeneic lymphocyte interaction. V. Identification and characterization of two components of allogeneic effect factor, one of which displays H-2-restricted helper activity and the other, T cell-growth factor activity.

1981 ◽  
Vol 153 (1) ◽  
pp. 107-128 ◽  
Author(s):  
T L Delovitch ◽  
J Watson ◽  
R Battistella ◽  
J F Harris ◽  
J Shaw ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
Spleen Cells ◽  
Con A ◽  
Effect Factor ◽  
T Cell Growth Factor

An allogeneic effect factor (AEF) derived from mixed lymphocyte reaction (MLR) cultures of alloactivated A.SW (H-2s) responder T cells and irradiated A/WySn (H-2a) stimulator spleen cells helps an in vitro primary anti-erythrocyte plaque-forming cell PFC response of BALB/c nude spleen cels and also A/WySn but not A.SW T cell-depleted spleen cells. AEF activity is adsorbed by anti-Ik and anti-I-Ak but not by anti-I-Jk, anti-I-ECk, and anti-Is. Gel filtration of ACA 54 resolves AEF into two main components that which appear in the 50,000- to 70,000-mol wt (component I) and 30,000- to 35,000-mol wt (component II) regions, respectively. Component I has a mol wt of 68,000, elutes from DEAE-Sephacel at 0.05-0.1 M NaCl, and has an isoelectric point (pI) of 5.8. It helps A/WySn but not A.SW B cells and, therefore, is H-2 restricted. Component II is not H-2 restricted, because it helps both A.SW and A/WySn B cells. It also stimulates (a) the growth of a long-term cytotoxic cell line in vitro, (b) Con A-induced thymocyte mitogenesis, and (c) the generation of cytotoxic T cells. The latter three properties of component II are not shared by component I. In addition, component II elutes from DEAE-Sephacel at 0.15-0.2 M NaCl and has a pI of 4.3 and 4.9. Ia determinants and Ig VH, CH, L-chain, and idiotypic determinants are not present on either component I or component II. The properties of component II are identical to that of a T cell growth factor produced by Con A-stimulated spleen cells. It is suggested that the H-2-restricted component I of AEF might be an MLR-activated responder T cell-derived Ia alloantigen receptor.

scholarly journals Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells.

1985 ◽  
Vol 162 (3) ◽  
pp. 979-992 ◽  
Author(s):  
T Maier ◽  
J H Holda ◽  
H N Claman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
Con A ◽  
In Vitro Expression ◽  
Graft Vs Host Disease ◽  
In Vivo Induction

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.

scholarly journals T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2894-2902 ◽  
Author(s):  
Jonathan A. Deane ◽  
Michael G. Kharas ◽  
Jean S. Oak ◽  
Linda N. Stiles ◽  
Ji Luo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
Pi3k Signaling ◽  
Regulatory Subunits ◽  
Cell Functions ◽  
Phosphoinositide 3 Kinase

Abstract The class IA subgroup of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, costimulatory molecules, and cytokine receptors on lymphocytes. Targeted deletion of individual genes for class IA regulatory subunits severely impairs the development and function of B cells but not T cells. Here we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85α, p55α, p50α, and p85β. These cells exhibit nearly complete loss of PI3K signaling downstream of the T-cell receptor (TCR) and CD28. Nevertheless, T-cell development is largely unperturbed, and peripheral T cells show only partial impairments in proliferation and cytokine production in vitro. Both genetic and pharmacologic experiments suggest that class IA PI3K signaling plays a limited role in T-cell proliferation driven by TCR/CD28 clustering. In vivo, class IA–deficient T cells provide reduced help to B cells but show normal ability to mediate antiviral immunity. Together these findings provide definitive evidence that class IA PI3K regulatory subunits are essential for a subset of T-cell functions while challenging the notion that this signaling mechanism is a critical mediator of costimulatory signals downstream of CD28.

Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location

1993 ◽  
Vol 13 (8) ◽  
pp. 4760-4769
Author(s):  
R J Bram ◽  
D T Hung ◽  
P K Martin ◽  
S L Schreiber ◽  
G R Crabtree
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Cyclosporin A ◽  
Cell Function ◽  
Inhibitory Effects ◽  
Gene Deletions ◽  
Cyclophilin B ◽  
Intracellular Vesicles

The immunosuppressants cyclosporin A (CsA) and FK506 appear to block T-cell function by inhibiting the calcium-regulated phosphatase calcineurin. While multiple distinct intracellular receptors for these drugs (cyclophilins and FKBPs, collectively immunophilins) have been characterized, the functionally active ones have not been discerned. We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. In contrast, cyclophilin C, FKBP13, and FKBP25 had no effect. Direct comparison of the Ki of each drug-immunophilin complex for calcineurin in vitro revealed that although calcineurin binding was clearly necessary, it was not sufficient to explain the in vivo activity of the immunophilin. Subcellular localization was shown also to play a role, since gene deletions of cyclophilins B and C which changed their intracellular locations altered their activities significantly. Cyclophilin B has been shown previously to be located within calcium-containing intracellular vesicles; its ability to mediate CsA inhibition implies that certain components of the signal transduction machinery are also spatially restricted within the cell.

scholarly journals The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays.

1980 ◽  
Vol 152 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Region Gene ◽  
Immunoglobulin Receptor

The mode of action by bystander helper T cells was investigated by priming (responder X nonresponder) (B6A)F1 T cells with poly-L-(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(TG)-A--L] and titrating the ability of these cells to stimulate an anti-sheep red blood cell (SRBC) response of parental B cells and macrophages in the presence of (TG)-A--L. Under limiting T cell conditions, and in the presence of (TG)-A--L, (TG)-A--L-responsive T cells were able to drive anti-SRBC responses of high-responder C57BL/10.SgSn (B10) B cells and macrophages (M0), but not of low-responder (B10.A) B cells and M0. Surprisingly, the (TG)-A--L-driven anti-SRBC response of B10.A B cells was not restored by addition of high-responder acessory cells, in the form of (B6A)F1 peritoneal or irradiated T cell-depleted spleen cells, or in the form of B10 nonirradiated T cell-depleted spleen cells. These results suggested that (TG)-A--L-specific Ir genes expressed by B cells controlled the ability of these cells to be induced to respond to SRBC by (TG)-A--L-responding T cells, implying that direct contact between the SRBC-binding B cell precursor and the (TG)-A--L-responsive helper T cells was required. Analogous results were obtained for keyhold limpet hemocyanin (KLH)-driven bystander help using KLH-primed F1 T cells restricted to interact with cells on only one of the parental haplotypes by maturing them in parental bone marrow chimeras. It was hypothesized that bystander help was mediated by nonspecific uptake of antigen [(TG)-A--L or KLH] by SRBC-specific b cells and subsequent display of the antigen on the B cell surface in association with Ir of I-region gene products, in a fashion similar to the M0, where it was then recognized by helper T cells. Such an explanation was supported by the observation that high concentrations of antigen were required to elicit bystander help. This hypothesis raises the possibility of B cell processing of antigen bound to its immunoglobulin receptor and subsequent presentation of antigen to helper T cells.

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