Abstract
Mouse CD38 has been implicated in the regulation of both B-cell proliferation and protection of B cells from irradiation-induced apoptosis. CD38 ligation on B cells by CS/2, an anti-mouse CD38 monoclonal antibody, induced proliferation, IgM secretion, and tyrosine phosphorylation of Bruton tyrosine kinase in B cells from wild-type mice. B cells from X chromosome-linked immunodeficient mice did not respond at all to anti-CD38 antibody, although CD38 expression on these B cells was comparable to that on wild-type B cells. We infer from these results that Bruton tyrosine kinase activation is involved in B-cell triggering after cross-linkage of CD38. Analysis of the synergistic effects of various cytokines with CD38 ligation on B-cell activation revealed that interleukin 5 (IL-5) showed the most potent effect on B-cell proliferation, Blimp1 gene expression, and IgM production. These synergistic effects were not seen with B cells from X chromosome-linked immunodeficient mice. Flow cytometry analysis revealed that CD38 ligation increased surface expression of the IL-5-receptor alpha chain on B cells. These data indicate that CD38 ligation increases IL-5 receptor alpha expression and synergizes with IL-5 to enhance Blimp1 expression and IgM synthesis.
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- Alexandropoulos K., Cheng G., Baltimore D. Proline-rich sequences that bind to Src homology 3 domains with individual specificities. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3110–3114. doi: 10.1073/pnas.92.8.3110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng G., Ye Z. S., Baltimore D. Binding of Bruton's tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8152–8155. doi: 10.1073/pnas.91.17.8152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Devos R., Plaetinck G., Van der Heyden J., Cornelis S., Vandekerckhove J., Fiers W., Tavernier J. Molecular basis of a high affinity murine interleukin-5 receptor. EMBO J. 1991 Aug;10(8):2133–2137. doi: 10.1002/j.1460-2075.1991.tb07747.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gelman L., Deterre P., Gouy H., Boumsell L., Debré P., Bismuth G. The lymphocyte surface antigen CD38 acts as a nicotinamide adenine dinucleotide glycohydrolase in human T lymphocytes. Eur J Immunol. 1993 Dec;23(12):3361–3364. doi: 10.1002/eji.1830231245. [DOI] [PubMed] [Google Scholar]
- Go N. F., Castle B. E., Barrett R., Kastelein R., Dang W., Mosmann T. R., Moore K. W., Howard M. Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med. 1990 Dec 1;172(6):1625–1631. doi: 10.1084/jem.172.6.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harada N., Santos-Argumedo L., Chang R., Grimaldi J. C., Lund F. E., Brannan C. I., Copeland N. G., Jenkins N. A., Heath A. W., Parkhouse R. M. Expression cloning of a cDNA encoding a novel murine B cell activation marker. Homology to human CD38. J Immunol. 1993 Sep 15;151(6):3111–3118. [PubMed] [Google Scholar]
- Hasbold J., Klaus G. G. B cells from CBA/N mice do not proliferate following ligation of CD40. Eur J Immunol. 1994 Jan;24(1):152–157. doi: 10.1002/eji.1830240123. [DOI] [PubMed] [Google Scholar]
- Hayashida K., Kitamura T., Gorman D. M., Arai K., Yokota T., Miyajima A. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9655–9659. doi: 10.1073/pnas.87.24.9655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hitoshi Y., Sonoda E., Kikuchi Y., Yonehara S., Nakauchi H., Takatsu K. IL-5 receptor positive B cells, but not eosinophils, are functionally and numerically influenced in mice carrying the X-linked immune defect. Int Immunol. 1993 Sep;5(9):1183–1190. doi: 10.1093/intimm/5.9.1183. [DOI] [PubMed] [Google Scholar]
- Howard M., Grimaldi J. C., Bazan J. F., Lund F. E., Santos-Argumedo L., Parkhouse R. M., Walseth T. F., Lee H. C. Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science. 1993 Nov 12;262(5136):1056–1059. doi: 10.1126/science.8235624. [DOI] [PubMed] [Google Scholar]
- Howard M., Pesavento P., Stein P. LPS-activated CBA/N mouse B cells respond to anti-Ig and a BSF-1-like factor. J Immunol. 1986 Jun 15;136(12):4531–4537. [PubMed] [Google Scholar]
- Ihle J. N., Witthuhn B. A., Quelle F. W., Yamamoto K., Thierfelder W. E., Kreider B., Silvennoinen O. Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci. 1994 May;19(5):222–227. doi: 10.1016/0968-0004(94)90026-4. [DOI] [PubMed] [Google Scholar]
- Kirkham P. A., Santos-Argumedo L., Harnett M. M., Parkhouse R. M. Murine B-cell activation via CD38 and protein tyrosine phosphorylation. Immunology. 1994 Dec;83(4):513–516. [PMC free article] [PubMed] [Google Scholar]
- Kitamura T., Sato N., Arai K., Miyajima A. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Cell. 1991 Sep 20;66(6):1165–1174. doi: 10.1016/0092-8674(91)90039-2. [DOI] [PubMed] [Google Scholar]
- Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
- Koike M., Kikuchi Y., Tominaga A., Takaki S., Akagi K., Miyazaki J., Yamamura K., Takatsu K. Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice. Int Immunol. 1995 Jan;7(1):21–30. doi: 10.1093/intimm/7.1.21. [DOI] [PubMed] [Google Scholar]
- Lund F. E., Solvason N. W., Cooke M. P., Health A. W., Grimaldi J. C., Parkhouse R. M., Goodnow C. C., Howard M. C. Signaling through murine CD38 is impaired in antigen receptor-unresponsive B cells. Eur J Immunol. 1995 May;25(5):1338–1345. doi: 10.1002/eji.1830250531. [DOI] [PubMed] [Google Scholar]
- Malavasi F., Funaro A., Roggero S., Horenstein A., Calosso L., Mehta K. Human CD38: a glycoprotein in search of a function. Immunol Today. 1994 Mar;15(3):95–97. doi: 10.1016/0167-5699(94)90148-1. [DOI] [PubMed] [Google Scholar]
- Mita S., Tominaga A., Hitoshi Y., Sakamoto K., Honjo T., Akagi M., Kikuchi Y., Yamaguchi N., Takatsu K. Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2311–2315. doi: 10.1073/pnas.86.7.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyake K., Yamashita Y., Hitoshi Y., Takatsu K., Kimoto M. Murine B cell proliferation and protection from apoptosis with an antibody against a 105-kD molecule: unresponsiveness of X-linked immunodeficient B cells. J Exp Med. 1994 Oct 1;180(4):1217–1224. doi: 10.1084/jem.180.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murata Y., Takaki S., Migita M., Kikuchi Y., Tominaga A., Takatsu K. Molecular cloning and expression of the human interleukin 5 receptor. J Exp Med. 1992 Feb 1;175(2):341–351. doi: 10.1084/jem.175.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rawlings D. J., Saffran D. C., Tsukada S., Largaespada D. A., Grimaldi J. C., Cohen L., Mohr R. N., Bazan J. F., Howard M., Copeland N. G. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science. 1993 Jul 16;261(5119):358–361. doi: 10.1126/science.8332901. [DOI] [PubMed] [Google Scholar]
- Santos-Argumedo L., Lund F. E., Heath A. W., Solvason N., Wu W. W., Grimaldi J. C., Parkhouse R. M., Howard M. CD38 unresponsiveness of xid B cells implicates Bruton's tyrosine kinase (btk) as a regular of CD38 induced signal transduction. Int Immunol. 1995 Feb;7(2):163–170. doi: 10.1093/intimm/7.2.163. [DOI] [PubMed] [Google Scholar]
- Santos-Argumedo L., Teixeira C., Preece G., Kirkham P. A., Parkhouse R. M. A B lymphocyte surface molecule mediating activation and protection from apoptosis via calcium channels. J Immunol. 1993 Sep 15;151(6):3119–3130. [PubMed] [Google Scholar]
- Sato S., Katagiri T., Takaki S., Kikuchi Y., Hitoshi Y., Yonehara S., Tsukada S., Kitamura D., Watanabe T., Witte O. IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and Janus 2 kinases. J Exp Med. 1994 Dec 1;180(6):2101–2111. doi: 10.1084/jem.180.6.2101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scher I., Ahmed A., Strong D. M., Steinberg A. D., Paul W. E. X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells. J Exp Med. 1975 Apr 1;141(4):788–803. [PMC free article] [PubMed] [Google Scholar]
- Scher I. CBA/N immune defective mice; evidence for the failure of a B cell subpopulation to be expressed. Immunol Rev. 1982;64:117–136. doi: 10.1111/j.1600-065x.1982.tb00421.x. [DOI] [PubMed] [Google Scholar]
- Takaki S., Kanazawa H., Shiiba M., Takatsu K. A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction. Mol Cell Biol. 1994 Nov;14(11):7404–7413. doi: 10.1128/mcb.14.11.7404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takaki S., Mita S., Kitamura T., Yonehara S., Yamaguchi N., Tominaga A., Miyajima A., Takatsu K. Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. EMBO J. 1991 Oct;10(10):2833–2838. doi: 10.1002/j.1460-2075.1991.tb07832.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takaki S., Murata Y., Kitamura T., Miyajima A., Tominaga A., Takatsu K. Reconstitution of the functional receptors for murine and human interleukin 5. J Exp Med. 1993 Jun 1;177(6):1523–1529. doi: 10.1084/jem.177.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takaki S., Tominaga A., Hitoshi Y., Mita S., Sonoda E., Yamaguchi N., Takatsu K. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990 Dec;9(13):4367–4374. doi: 10.1002/j.1460-2075.1990.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takatsu K. Interleukin-5. Curr Opin Immunol. 1992 Jun;4(3):299–306. doi: 10.1016/0952-7915(92)90080-x. [DOI] [PubMed] [Google Scholar]
- Takatsu K., Takaki S., Hitoshi Y. Interleukin-5 and its receptor system: implications in the immune system and inflammation. Adv Immunol. 1994;57:145–190. doi: 10.1016/s0065-2776(08)60673-2. [DOI] [PubMed] [Google Scholar]
- Tavernier J., Devos R., Cornelis S., Tuypens T., Van der Heyden J., Fiers W., Plaetinck G. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell. 1991 Sep 20;66(6):1175–1184. doi: 10.1016/0092-8674(91)90040-6. [DOI] [PubMed] [Google Scholar]
- Thomas J. D., Sideras P., Smith C. I., Vorechovský I., Chapman V., Paul W. E. Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. Science. 1993 Jul 16;261(5119):355–358. doi: 10.1126/science.8332900. [DOI] [PubMed] [Google Scholar]
- Touhara K., Inglese J., Pitcher J. A., Shaw G., Lefkowitz R. J. Binding of G protein beta gamma-subunits to pleckstrin homology domains. J Biol Chem. 1994 Apr 8;269(14):10217–10220. [PubMed] [Google Scholar]
- Tsukada S., Rawlings D. J., Witte O. N. Role of Bruton's tyrosine kinase in immunodeficiency. Curr Opin Immunol. 1994 Aug;6(4):623–630. doi: 10.1016/0952-7915(94)90151-1. [DOI] [PubMed] [Google Scholar]
- Tsukada S., Saffran D. C., Rawlings D. J., Parolini O., Allen R. C., Klisak I., Sparkes R. S., Kubagawa H., Mohandas T., Quan S. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993 Jan 29;72(2):279–290. doi: 10.1016/0092-8674(93)90667-f. [DOI] [PubMed] [Google Scholar]
- Tsukada S., Simon M. I., Witte O. N., Katz A. Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11256–11260. doi: 10.1073/pnas.91.23.11256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turner C. A., Jr, Mack D. H., Davis M. M. Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell. 1994 Apr 22;77(2):297–306. doi: 10.1016/0092-8674(94)90321-2. [DOI] [PubMed] [Google Scholar]
- Yamaguchi N., Hitoshi Y., Mita S., Hosoya Y., Murata Y., Kikuchi Y., Tominaga A., Takatsu K. Characterization of the murine interleukin 5 receptor by using a monoclonal antibody. Int Immunol. 1990;2(2):181–187. doi: 10.1093/intimm/2.2.181. [DOI] [PubMed] [Google Scholar]
- Yamashita Y., Miyake K., Kikuchi Y., Takatsu K., Noda S., Kosugi A., Kimoto M. A monoclonal antibody against a murine CD38 homologue delivers a signal to B cells for prolongation of survival and protection against apoptosis in vitro: unresponsiveness of X-linked immunodeficient B cells. Immunology. 1995 Jun;85(2):248–255. [PMC free article] [PubMed] [Google Scholar]
- Yao L., Kawakami Y., Kawakami T. The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9175–9179. doi: 10.1073/pnas.91.19.9175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zocchi E., Franco L., Guida L., Benatti U., Bargellesi A., Malavasi F., Lee H. C., De Flora A. A single protein immunologically identified as CD38 displays NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer surface of human erythrocytes. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1459–1465. doi: 10.1006/bbrc.1993.2416. [DOI] [PubMed] [Google Scholar]