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J Exp Med. 1993 Apr 1; 177(4): 925–935.
PMCID: PMC2190967

Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal

Abstract

Cognate interactions between antigen-presenting B and T cells play crucial roles in immunologic responses. T cells that have been activated via the crosslinking of CD3 are able to induce B cell proliferation and immunoglobulin secretion in a major histocompatibility complex-unrestricted and contact-dependent manner. We find that such activated human CD4+ T cells, but not control Ig- treated T cells, may induce normal or leukemic B cells to express B7/BB1 and significantly higher levels of CD54 intercellular adhesion molecule 1 via a process that also requires direct cell-cell contact. To discern what cell surface molecule(s) may be responsible for signalling B cells to express B7/BB1, we added various monoclonal antibodies (mAbs) specific for T or B cell accessory molecules or control mAbs to cocultures of alpha-CD3-activated T cells and resting B cells. We find that only alpha-CD40 mAbs can significantly inhibit the increased expression of B7/BB1, suggesting that the ligand for CD40 expressed on activated T cells may be an important inducer of B7/BB1 expression. Subsequent experiments in fact demonstrate that alpha-CD40 mAbs, but not control mAbs, induce changes in B cell phenotype similar to those induced by activated T cells when the mAbs are presented on Fc gamma RII (CDw32)-expressing L cells. These phenotypic changes have significant effects on B cell function. Whereas chronic lymphocytic leukemia (CLL) B cells normally are very poor stimulators in allogeneic mixed lymphocyte reactions (MLRs), CLL-B cells preactivated via CD40 crosslinking are significantly better presenters of alloantigen, affecting up to 30-fold-greater stimulation of T cell proliferation than that induced by control treated or nontreated CLL-B cells. Similarly, the MLR of T cells stimulated by allogeneic nonleukemic B cells can be enhanced significantly if the stimulator B cells are preactivated via CD40 crosslinking. The enhanced MLR generated by such preactivated B cells may be inhibited by blocking B7/BB1-CD28 interaction with CTLA4Ig. These studies demonstrate a novel, CD40- dependent pathway for inducing B cell expression of B7/BB1 and enhancing B cell antigen-presenting cell activity that can be initiated via cell-cell contact with alpha-CD3-stimulated CD4+ T cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. [PubMed]
  • Kurt-Jones EA, Liano D, HayGlass KA, Benacerraf B, Sy MS, Abbas AK. The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice. J Immunol. 1988 Jun 1;140(11):3773–3778. [PubMed]
  • Janeway CA, Jr, Ron J, Katz ME. The B cell is the initiating antigen-presenting cell in peripheral lymph nodes. J Immunol. 1987 Feb 15;138(4):1051–1055. [PubMed]
  • Ron Y, Sprent J. T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes. J Immunol. 1987 May 1;138(9):2848–2856. [PubMed]
  • Abbas AK, Haber S, Rock KL. Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors. J Immunol. 1985 Sep;135(3):1661–1667. [PubMed]
  • Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. [PubMed]
  • Inaba K, Steinman RM. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. [PMC free article] [PubMed]
  • Metlay JP, Puré E, Steinman RM. Distinct features of dendritic cells and anti-Ig activated B cells as stimulators of the primary mixed leukocyte reaction. J Exp Med. 1989 Jan 1;169(1):239–254. [PMC free article] [PubMed]
  • Frohman M, Cowing C. Presentation of antigen by B cells: functional dependence on radiation dose, interleukins, cellular activation, and differential glycosylation. J Immunol. 1985 Apr;134(4):2269–2275. [PubMed]
  • Eynon EE, Parker DC. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J Exp Med. 1992 Jan 1;175(1):131–138. [PMC free article] [PubMed]
  • Damle NK, Klussman K, Linsley PS, Aruffo A. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol. 1992 Apr 1;148(7):1985–1992. [PubMed]
  • Sanders VM, Vitetta ES. B cell-associated LFA-1 and T cell-associated ICAM-1 transiently cluster in the area of contact between interacting cells. Cell Immunol. 1991 Jan;132(1):45–55. [PubMed]
  • Sanders VM, Snyder JM, Uhr JW, Vitetta ES. Characterization of the physical interaction between antigen-specific B and T cells. J Immunol. 1986 Oct 15;137(8):2395–2404. [PubMed]
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]
  • Freeman GJ, Freedman AS, Segil JM, Lee G, Whitman JF, Nadler LM. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol. 1989 Oct 15;143(8):2714–2722. [PubMed]
  • Freedman AS, Freeman G, Horowitz JC, Daley J, Nadler LM. B7, a B-cell-restricted antigen that identifies preactivated B cells. J Immunol. 1987 Nov 15;139(10):3260–3267. [PubMed]
  • Koulova L, Clark EA, Shu G, Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med. 1991 Mar 1;173(3):759–762. [PMC free article] [PubMed]
  • Azuma M, Cayabyab M, Buck D, Phillips JH, Lanier LL. CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med. 1992 Feb 1;175(2):353–360. [PMC free article] [PubMed]
  • Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med. 1991 Mar 1;173(3):721–730. [PMC free article] [PubMed]
  • Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. [PubMed]
  • Hirohata S, Jelinek DF, Lipsky PE. T cell-dependent activation of B cell proliferation and differentiation by immobilized monoclonal antibodies to CD3. J Immunol. 1988 Jun 1;140(11):3736–3744. [PubMed]
  • Noelle RJ, McCann J, Marshall L, Bartlett WC. Cognate interactions between helper T cells and B cells. III. Contact-dependent, lymphokine-independent induction of B cell cycle entry by activated helper T cells. J Immunol. 1989 Sep 15;143(6):1807–1814. [PubMed]
  • Hodgkin PD, Yamashita LC, Coffman RL, Kehry MR. Separation of events mediating B cell proliferation and Ig production by using T cell membranes and lymphokines. J Immunol. 1990 Oct 1;145(7):2025–2034. [PubMed]
  • Noelle RJ, Daum J, Bartlett WC, McCann J, Shepherd DM. Cognate interactions between helper T cells and B cells. V. Reconstitution of T helper cell function using purified plasma membranes from activated Th1 and Th2 T helper cells and lymphokines. J Immunol. 1991 Feb 15;146(4):1118–1124. [PubMed]
  • Tohma S, Lipsky PE. Analysis of the mechanisms of T cell-dependent polyclonal activation of human B cells. Induction of human B cell responses by fixed activated T cells. J Immunol. 1991 Apr 15;146(8):2544–2552. [PubMed]
  • Vernino L, McAnally LM, Ramberg J, Lipsky PE. Generation of nondividing high rate Ig-secreting plasma cells in cultures of human B cells stimulated with anti-CD3-activated T cells. J Immunol. 1992 Jan 15;148(2):404–410. [PubMed]
  • Whalen BJ, Tony HP, Parker DC. Characterization of the effector mechanism of help for antigen-presenting and bystander resting B cell growth mediated by Ia-restricted Th2 helper T cell lines. J Immunol. 1988 Oct 1;141(7):2230–2239. [PubMed]
  • Freedman AS, Boyd AW, Bieber FR, Daley J, Rosen K, Horowitz JC, Levy DN, Nadler LM. Normal cellular counterparts of B cell chronic lymphocytic leukemia. Blood. 1987 Aug;70(2):418–427. [PubMed]
  • Kipps TJ. The CD5 B cell. Adv Immunol. 1989;47:117–185. [PubMed]
  • Foon KA, Rai KR, Gale RP. Chronic lymphocytic leukemia: new insights into biology and therapy. Ann Intern Med. 1990 Oct 1;113(7):525–539. [PubMed]
  • Kay NE, Perri RT. Immunobiology of malignant B cells and immunoregulatory cells in B-chronic lymphocytic leukemia. Clin Lab Med. 1988 Mar;8(1):163–177. [PubMed]
  • Han T, Bloom ML, Dadey B, Bennett G, Minowada J, Sandberg AA, Ozer H. Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status. Blood. 1982 Nov;60(5):1075–1081. [PubMed]
  • Wolos JA, Davey FR. Depressed stimulation in the MLR by B lymphocytes on chronic lymphocytic leukemia: failure to demonstrate a suppressor cell. Clin Immunol Immunopathol. 1979 Sep;14(1):77–85. [PubMed]
  • Inghirami G, Wieczorek R, Zhu BY, Silber R, Dalla-Favera R, Knowles DM. Differential expression of LFA-1 molecules in non-Hodgkin's lymphoma and lymphoid leukemia. Blood. 1988 Oct;72(4):1431–1434. [PubMed]
  • Baldini L, Cro L, Calori R, Nobili L, Silvestris I, Maiolo AT. Differential expression of very late activation antigen-3 (VLA-3)/VLA-4 in B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. Blood. 1992 May 15;79(10):2688–2693. [PubMed]
  • Clark EA, Ledbetter JA. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. [PMC free article] [PubMed]
  • Kipps TJ, Meisenholder G, Robbins BA. New developments in flow cytometric analyses of lymphocyte markers. Clin Lab Med. 1992 Jun;12(2):237–275. [PubMed]
  • Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561–569. [PMC free article] [PubMed]
  • Geppert TD, Lipsky PE. Immobilized anti-CD3-induced T cell growth: comparison of the frequency of responding cells within various T cell subsets. Cell Immunol. 1991 Mar;133(1):206–218. [PubMed]
  • Ko HS, Fu SM, Winchester RJ, Yu DT, Kunkel HG. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. [PMC free article] [PubMed]
  • Oshima S, Eckels DD. Selective signal transduction through the CD3 or CD2 complex is required for class II MHC expression by human T cells. J Immunol. 1990 Dec 15;145(12):4018–4025. [PubMed]
  • Stohl W, Posnett DN, Chiorazzi N. Induction of T cell-dependent B cell differentiation by anti-CD3 monoclonal antibodies. J Immunol. 1987 Mar 15;138(6):1667–1673. [PubMed]
  • Mustelin T, Coggeshall KM, Isakov N, Altman A. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation. Science. 1990 Mar 30;247(4950):1584–1587. [PubMed]
  • June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF, Samelson LE. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722–7726. [PMC free article] [PubMed]
  • Barrett TB, Shu G, Clark EA. CD40 signaling activates CD11a/CD18 (LFA-1)-mediated adhesion in B cells. J Immunol. 1991 Mar 15;146(6):1722–1729. [PubMed]
  • Noelle RJ, Roy M, Shepherd DM, Stamenkovic I, Ledbetter JA, Aruffo A. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550–6554. [PMC free article] [PubMed]
  • Rousset F, Garcia E, Banchereau J. Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J Exp Med. 1991 Mar 1;173(3):705–710. [PMC free article] [PubMed]
  • Clark EA, Shu GL, Lüscher B, Draves KE, Banchereau J, Ledbetter JA, Valentine MA. Activation of human B cells. Comparison of the signal transduced by IL-4 to four different competence signals. J Immunol. 1989 Dec 15;143(12):3873–3880. [PubMed]
  • Inaba K, Steinman RM. Protein-specific helper T-lymphocyte formation initiated by dendritic cells. Science. 1985 Aug 2;229(4712):475–479. [PubMed]
  • Linsley PS, Wallace PM, Johnson J, Gibson MG, Greene JL, Ledbetter JA, Singh C, Tepper MA. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992 Aug 7;257(5071):792–795. [PubMed]
  • Young JW, Koulova L, Soergel SA, Clark EA, Steinman RM, Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992 Jul;90(1):229–237. [PMC free article] [PubMed]
  • Galy AH, Spits H. CD40 is functionally expressed on human thymic epithelial cells. J Immunol. 1992 Aug 1;149(3):775–782. [PubMed]
  • Freudenthal PS, Steinman RM. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. [PMC free article] [PubMed]
  • Lin RH, Mamula MJ, Hardin JA, Janeway CA., Jr Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991 Jun 1;173(6):1433–1439. [PMC free article] [PubMed]
  • Mamula MJ, Lin RH, Janeway CA, Jr, Hardin JA. Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c. J Immunol. 1992 Aug 1;149(3):789–795. [PubMed]
  • Taurog JD, Kerwar SS, McReynolds RA, Sandberg GP, Leary SL, Mahowald ML. Synergy between adjuvant arthritis and collagen-induced arthritis in rats. J Exp Med. 1985 Sep 1;162(3):962–978. [PMC free article] [PubMed]
  • Seki N, Sudo Y, Yoshioka T, Sugihara S, Fujitsu T, Sakuma S, Ogawa T, Hamaoka T, Senoh H, Fujiwara H. Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity. J Immunol. 1988 Mar 1;140(5):1477–1484. [PubMed]

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