摘要:

AbstractThe B1 cell surface molecule (CD20) is a 35‐kDa phosphoprotein expressed by B lineage cells during most stages of differentiation. Some monoclonal antibodies reactive with B1 induce activation while others, anti‐B1a, inhibit B lymphocyte function. To further determine the requirement of B1 molecule function in proliferation and differentiation the effects of anti‐B1a antibody binding on early cellular activation events were examined. Immunoglobulin secretion of lymphocyte cultures stimulated with pokeweed mitogen was maximally inhibited if the antibody (1‐10μg/ml) was added during the first 24 h of culture. However, even high antibody concentrations were unable to inhibit increases in free intracellular Ca2+concentrations immediately following cross‐linkage of cell surface immunoglobulin, or inhibit cell enlargement and the expression of transferrin and interleukin 2 receptors. Antibody binding to B1 inhibited RNA synthesis (37‐80%) and progression through cell cycle following activation. In contrast, proliferation induced by phorbol myristate acetate was not inhibited by antibody binding to the B1 molecule. The findings that the earliest activation events and phorbol myristate acetate‐induced proliferation were not inhibited by antibody binding to B1 suggest that inhibition is due to the blocking of a step of the activation process required for cell cycle progression and differentiation, rather than blocking initial signal transduction across the membrane or providing a negative or supp

ISSN:0014-2980    

DOI:10.1002/eji.1830160802

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractIn the present study we have investigated the structure of the helper T cell (Th)‐defined idiotope (Id) of myeloma protein 315 λ2 light chain (λ2315) in BALB/c (H‐2d) mice which carry a high‐responder immune response gene for this Id. Three eptides were synthesized which spanned the third hypervariable region (HV3) of λ2315: peptides 88–99, 94–108 and 91–108. Only peptide 91–108 was capable of eliciting carrier‐specific Ththat recognized M315 or free λ2315. These Thdid not recognize λ25–7chain which differs from λ2315at 4 positions in this region; these are Tyr94, Ser95, Thr96, Tyr98for λ25–7and Phe94, Arg95, Asn96, Phe98for λ2315. Immunization with peptide analogues revealed that substitution of Tyr for Phe94was compatible with Id‐λ2315mimicry, but substitution of Ser for Arg95or Thr for Asn96destroyed the Th‐recognized Id. Furthermore, Thprimed with λ25–7chain did not cross‐react with λ2T952these λ2 chains only differ from each other at positions 98 and 99 at the Vλ2‐Jλ2 junction. The data indicate that individual amino acids of short peptide segments are critical for Th‐recognized Id of the λ2 HV3 loop and Vλ2‐Jλ2 junction. Furthermore, the immunogenicity of a small peptide suggests that the carrier (λ2)‐specific Threcognize Id that have been processed by antigen‐presenting cells (APC). This implies the existence of two categories of “internal images” of foreign or of self antigens: (a) serologically defined and (b) T lymphocyte defined. We propose that as a rule, Id processing by APC, including B cells, destroys the first and reveals the second category. The possible physiological function of these Id‐speci

ISSN:0014-2980    

DOI:10.1002/eji.1830160803

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe diversity of λ variable (Vλ) domains is extremely restricted when compared to those of VHand Vλ. In addition, each Vλdomain is determined by the Cλdomain, For these reasons, the λ system is an excellent model for the study of the associated VHregion repertoire. The study of Vλdomain diversity has been limited by the small contribution (approximately 5%) of λ‐bearing proteins to the total Ig pool. We now show that treatment of BALB/c mice with rabbit anti‐λ1 antibodies coupled to lipopolysaccharide induces a production of polyclonal λ1 light chain‐bearing Ig whereas, conversely, treatment with rabbit anti‐λ2 antibodies induces a production of polyclonal λ2 + λ3 light chain‐bearing Ig. The antigenic specificities of these two distinct λ populations were then studied using B1355 dextran, (4‐hydroxy‐3‐nitrophenyl)acetyl (NP) and 2,4‐dinitrophenyl (DNP) as antigens. The anti‐α(1‐3)dextran antibody specificity was found to be mediated exclusively by antibodies bearing the λ1 isotype whereas the anti‐NP and anti‐DNP antibody specificities are mediated by both the λ1 and λ2 + λ3 isotypes. In addition, various mouse strains with the VHaor VHballotypic haplotype and the r λ110or r λ1+phenotype were treated with rabbit anti‐λ1 antibodies. The λ1 anti‐NP and anti‐DNP antibody specificities were similar in all strains whereas the λ1 anti‐α(1‐3)dextran specificity was linked to the presence of the VHaallotypic haplotype. The mouse strains with the r λ110or r λ1+phenotype

ISSN:0014-2980    

DOI:10.1002/eji.1830160804

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractSimultaneous expression of particular immunoglobulin Fc receptors (FcR) was studied on the plasma membranes of murine peritoneal macrophages. This was facilitated by the use of sheep red blood cells (SRBC) and/or synthetic microspheres coated with monoclonal antibodies of different isotypes. It was concluded that a majority of macrophages bear more than one type of FcR; macrophages bearing at least three types of FcR were present in the peritoneal cavity; macrophages bearing FcμR did not bind IgE, IgA or IgG; all macrophages bearing FcαR also expressed Fcγ2bR, Fcγ3R, and FcεR; all macrophages bearing FcεR also expressed Fcγ2bR and FcαR. Except for FcαR, essentially equivalent numbers of FcR‐bearing macrophages were detected when antibody‐coated SRBC or polymeric microspheres were used. Simultaneous applications of these reagents permitted the most detailed and direct investigations yet performed of multiple FcR expression on indi

ISSN:0014-2980    

DOI:10.1002/eji.1830160805

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractEntry of Ca2+into the cell is recognized as an important activation signal for mitogeninduced lymphocyte proliferation. Changes in free cytosolic Ca2+([Ca2+]i) can now be measured directly using the fluorescent reagent quin‐2. To analyze the role of [Ca2+]iin human T cell activation, we have determined the effect of the calcium channel blocker, nifedipine, on phytohemagglutinin (PHA)‐induced lymphocyte proliferation. At a concentration of 50 μM, nifedipine is nontoxic, and prevents PHA‐induced proliferation. In parallel the drug prevents the lectin‐induced increase in concentration of [Ca2+]iand interleukin 2 (IL2) secretion; IL2 receptor expression is unaffected. In the presence of exogenous IL2, cell proliferation proceeds normally. Treatment of the cells with the tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate prevents the inhibitory effect of nifedipine on cell proliferation. Since TPA is itself nonmitogenic and does not affect levels of cytosolic Ca2+, these data and the data on IL2 receptor expression indicate that PHA can generate an activation signal(s) which is [Ca2

ISSN:0014-2980    

DOI:10.1002/eji.1830160806

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractImmunity against lymphocytic choriomeningitis virus (LCMV) in anti‐IgM‐treated B cell‐depleted mice was evaluated. We found that the following immune phenomena were independent of antibodies: (a) the generation of virus‐specific cytotoxic T cells; (b) the footpad swelling response against locally injected LCMV; (c) natural killer cell activity basic levels or after LCMV or poly(1). poly(C) stimulation; (d) immunopathologically mediated LCM after primary intracerebral inoculation; (e) immunological memory in LCMV‐immune mice assessed by immune protection against LCM after intracerebrally injected virus or as resistance against the local footpad swelling response to LCMV. This study demonstrates that humoral immunity plays no crucial role in immune protection and immunopathology in murine LCMV infection and suggests that protective memory T cell function is B cell and antibody in

ISSN:0014-2980    

DOI:10.1002/eji.1830160807

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe immune response to the phosphorylcholine (PC) hapten elicited in BALB/c mice by PC‐keyhole limpet hemocyanin (KLH) is composed of 2 groups of antibodies with specificity to PC and phenyl‐PC, respectively. They were designated as group I and group II anti‐PC antibodies. In this report we demonstrate that anti‐PC IgE antibodies elicited by PC‐KLH or PC‐ovalbumin belong to the group II and do not express the T15 idiotype. Anti‐PC IgG1, IgG2a, and IgG2bantibodies express group I characteristics in the primary response and bear the T15 idiotype. Later, after 5 weeks and 3 injections of PC‐KLH or PC‐ovalbumin, a change in these isotypes to group II antibodies is observed. In contrast, anti‐PC IgE is a group II antibody throughout progression of the immune response. The regulation of group I and group II antibody expression in serum is independent of the genetic backgr

ISSN:0014-2980    

DOI:10.1002/eji.1830160808

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe roles of interleukin 2 (IL 2) and interferon‐γ (IFN‐γ) in human peripheral blood B cell activation, growth and differentiation were examined. Highly purified B cells stimulated with Cowan IStaphylococcus aureus(SA) proliferated minimally and generated no immunoglobulin‐secreting cells (ISC) without the addition of T cell supernatants (T sup) produced by mitogen‐activated T cells. Recombinant IL 2 (rIL 2) alone was able to promote maximum proliferation and generation of ISC in cultures of highly purified SA‐stimulated B cells when present from the initiation of the incubation. IFN‐γ, by contrast, could not support either response alone. When a twostep culture system was employed to determine the effect(s) of T cell influences during both initial activation and in propagating the response following activation, it was found that B cells activated by SA alone subsequently responded maximally to T sup but only minimally to IL 2 and not at all to IFN‐γ. However, the presence of T sup, rIL 2, or rIFN‐γ during initial activation with SA was found to facilitate greatly the subsequent capacity of the activated B cells to proliferate and differentiate in response to either T sup or IL 2. These data suggest two distinct pathways of human B cell responsiveness. Activities in T sup other than IL 2 or IFN‐γ can support the growth and differentiation of B cells initially activated with SA alone, whereas rIL 2 is capable of promoting these responses maximally only when B cells have been initially activated by SA in the presence of T cell lymphokines, such as IL 2 or IFN‐γ. The results emphasize the role of specific T cell factors in determining the outcome o

ISSN:0014-2980    

DOI:10.1002/eji.1830160809

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractAn important question in mitogen activation of T cells is whether the T cell must interact with a major histocompatibility complex product during the activation process. The T helper hybridoma AODH 7.1 is specific for human gamma globulin in the context of IEd, and when activated secretes interleukin 2. The mitogen concanavalin A (Con A) can activate AODH 7.1 cells directly, but two other standard T cell mitogens, phytohemagglutinin (PHA) and neuraminidase‐galactose oxidase, cannot. However, Con A, PHA and neuraminidase‐galactose oxidase could all activate AODH 7.1 when presented on various cloned class II+cell lines. There was an absolute requirement for the presentor cell to be class II+, and the activation signal on mitogen‐treated class II+presentor could be blocked by monoclonal antibody to the class II antigens. To determine if class II molecules were absolutely required for the presentation of a mitogen activation signal we used class II−LtK−L cells and two LtK−cell class II gene transformants as presentor cells. Only the class II+transformants, but not the class II−LtK−cells, could present either Con A or PHA. The class II requirement cannot be bypassed through provision of soluble factors. However, when Con A was used to activate AODH 7.1 cells directly, it appeared to be acting in a transmembrane fashion. It was not the case that AODH 7.1 cells were responding to Con A on a neighboring AODH 7.1 cell, and no class II antigens were involved. These results are consistent with the idea that different routes of activation exist for T cells, at least at the level of sig

ISSN:0014-2980    

DOI:10.1002/eji.1830160810

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractA cell transfer system was used to study the effect of anti‐Ia antibodies on anti‐DNA‐producing B cells. B cells from autoimmune New Zealand Black (NZB) mice were necessary and sufficient to transfer anti‐DNA antibody production to congenic NZB.xidrecipients. Anti‐Ia treatment of either donors or recipients led to a significant reduction in the number of B cells secreting anti‐DNA antibody. This effect was detectable after as little as 3 days of treatment and persisted for at least 1 month after the cessation of therapy. In this system, we could find no evidence of suppressor cell induction. These data suggest that anti‐Ia antibodies directly suppress autoantibody‐producin

ISSN:0014-2980    

DOI:10.1002/eji.1830160811

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY