Abstract
Transfectants of mature B cell lines that bind phosphorylcholine were made in order to understand the role of the COOH terminus of the mu chain of membrane IgM (mIgM) in generation of antigen-specific signals. A chimeric receptor (I-A alpha tail) was constructed by replacing 40 amino acids from the mu COOH terminus with that of major histocompatibility complex class II I-A alpha chain. The effect of wild- type and chimeric tails were studied on representative immediate-early antigen-specific signals. The I-A alpha tail hybrid, but not the wild- type receptor, was defective in antigen-driven Ca2+ mobilization, although it could effectively endocytose ligand-receptor complexes. Signal(s) transduced through the wild-type receptor led to transient induction of selected immediate-early gene messages (Egr-1, c-fos, Jun) above basal levels. However, the signal(s) generated after crosslinking of the I-A alpha tail receptor either showed no effect (c-fos) or actually repressed basal level expression of Egr-1 and Jun. Thus, we have established that receptor-mediated endocytosis can be distinguished from other early events associated with B cell activation, based on their differential dependence upon the structural fidelity of the COOH-terminal sequence of mIgM.
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- Antoine J. C., Avrameas S. Surface immunoglobulins of rat immunocytes: quantitation and fate of cell-bound peroxidase-labeled antibody and Fab fragment. Eur J Immunol. 1974 Jul;4(7):468–474. doi: 10.1002/eji.1830040705. [DOI] [PubMed] [Google Scholar]
- Ben-Nun A., Choi E., McIntyre K. R., Leeman S. A., McKean D. J., Seidman J. G., Glimcher L. H. DNA-mediated transfer of major histocompatibility class II I-Ab and I-Abm12 genes into B lymphoma cells: molecular and functional analysis of introduced antigens. J Immunol. 1985 Aug;135(2):1456–1464. [PubMed] [Google Scholar]
- Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. Regions of allelic hypervariability in the murine A alpha immune response gene. Cell. 1983 Aug;34(1):169–177. doi: 10.1016/0092-8674(83)90147-2. [DOI] [PubMed] [Google Scholar]
- Berridge M. J., Cobbold P. H., Cuthbertson K. S. Spatial and temporal aspects of cell signalling. Philos Trans R Soc Lond B Biol Sci. 1988 Jul 26;320(1199):325–343. doi: 10.1098/rstb.1988.0080. [DOI] [PubMed] [Google Scholar]
- Bishop G. A., Haughton G. Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7410–7414. doi: 10.1073/pnas.83.19.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cambier J. C., Ransom J. T. Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol. 1987;5:175–199. doi: 10.1146/annurev.iy.05.040187.001135. [DOI] [PubMed] [Google Scholar]
- Campbell K. S., Cambier J. C. B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex. EMBO J. 1990 Feb;9(2):441–448. doi: 10.1002/j.1460-2075.1990.tb08129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell M. A., Sefton B. M. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin. EMBO J. 1990 Jul;9(7):2125–2131. doi: 10.1002/j.1460-2075.1990.tb07381.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
- Chen J. Z., Stall A. M., Herzenberg L. A., Herzenberg L. A. Differences in glycoprotein complexes associated with IgM and IgD on normal murine B cells potentially enable transduction of different signals. EMBO J. 1990 Jul;9(7):2117–2124. doi: 10.1002/j.1460-2075.1990.tb07380.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu G., Hayakawa H., Berg P. Electroporation for the efficient transfection of mammalian cells with DNA. Nucleic Acids Res. 1987 Feb 11;15(3):1311–1326. doi: 10.1093/nar/15.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conzelman K. A., Mooseker M. S. The 110-kD protein-calmodulin complex of the intestinal microvillus is an actin-activated MgATPase. J Cell Biol. 1987 Jul;105(1):313–324. doi: 10.1083/jcb.105.1.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis L. S., Wacholtz M. C., Lipsky P. E. The induction of T cell unresponsiveness by rapidly modulating CD3. J Immunol. 1989 Feb 15;142(4):1084–1094. [PubMed] [Google Scholar]
- DeFranco A. L. Molecular aspects of B-lymphocyte activation. Annu Rev Cell Biol. 1987;3:143–178. doi: 10.1146/annurev.cb.03.110187.001043. [DOI] [PubMed] [Google Scholar]
- Drake J. R., Repasky E. A., Bankert R. B. Endocytosis of antigen, anti-idiotype, and anti-immunoglobulin antibodies and receptor re-expression by murine B cells. J Immunol. 1989 Sep 15;143(6):1768–1776. [PubMed] [Google Scholar]
- GRAHAM R. C., Jr, LUNDHOLM U., KARNOVSKY M. J. CYTOCHEMICAL DEMONSTRATION OF PEROXIDASE ACTIVITY WITH 3-AMINO-9-ETHYLCARBAZOLE. J Histochem Cytochem. 1965 Feb;13:150–152. doi: 10.1177/13.2.150. [DOI] [PubMed] [Google Scholar]
- Geiser J. R., van Tuinen D., Brockerhoff S. E., Neff M. M., Davis T. N. Can calmodulin function without binding calcium? Cell. 1991 Jun 14;65(6):949–959. doi: 10.1016/0092-8674(91)90547-c. [DOI] [PubMed] [Google Scholar]
- Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
- Gold M. R., Law D. A., DeFranco A. L. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor. Nature. 1990 Jun 28;345(6278):810–813. doi: 10.1038/345810a0. [DOI] [PubMed] [Google Scholar]
- Gold M. R., Matsuuchi L., Kelly R. B., DeFranco A. L. Tyrosine phosphorylation of components of the B-cell antigen receptors following receptor crosslinking. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3436–3440. doi: 10.1073/pnas.88.8.3436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Granger B. L., Lazarides E. Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle. Cell. 1980 Dec;22(3):727–738. doi: 10.1016/0092-8674(80)90549-8. [DOI] [PubMed] [Google Scholar]
- Greenlee D. V., Andreasen T. J., Storm D. R. Calcium-independent stimulation of Bordetella pertussis adenylate cyclase by calmodulin. Biochemistry. 1982 May 25;21(11):2759–2764. doi: 10.1021/bi00540a028. [DOI] [PubMed] [Google Scholar]
- Guise J. W., Lim P. L., Yuan D., Tucker P. W. Alternative expression of secreted and membrane forms of immunoglobulin mu-chain is regulated by transcriptional termination in stable plasmacytoma transfectants. J Immunol. 1988 Jun 1;140(11):3988–3994. [PubMed] [Google Scholar]
- Hombach J., Tsubata T., Leclercq L., Stappert H., Reth M. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature. 1990 Feb 22;343(6260):760–762. doi: 10.1038/343760a0. [DOI] [PubMed] [Google Scholar]
- Hurn B. A., Chantler S. M. Production of reagent antibodies. Methods Enzymol. 1980;70(A):104–142. doi: 10.1016/s0076-6879(80)70044-7. [DOI] [PubMed] [Google Scholar]
- Kearney J. F., Barletta R., Quan Z. S., Quintáns J. Monoclonal vs. heterogeneous anti-H-8 antibodies in the analysis of the anti-phosphorylcholine response in BALB/c mice. Eur J Immunol. 1981 Nov;11(11):877–883. doi: 10.1002/eji.1830111106. [DOI] [PubMed] [Google Scholar]
- Kim K. J., Kanellopoulos-Langevin C., Merwin R. M., Sachs D. H., Asofsky R. Establishment and characterization of BALB/c lymphoma lines with B cell properties. J Immunol. 1979 Feb;122(2):549–554. [PubMed] [Google Scholar]
- Kishimoto T. Factors affecting B-cell growth and differentiation. Annu Rev Immunol. 1985;3:133–157. doi: 10.1146/annurev.iy.03.040185.001025. [DOI] [PubMed] [Google Scholar]
- Klemsz M. J., Justement L. B., Palmer E., Cambier J. C. Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands. J Immunol. 1989 Aug 1;143(3):1032–1039. [PubMed] [Google Scholar]
- Page D. M., DeFranco A. L. Role of phosphoinositide-derived second messengers in mediating anti-IgM-induced growth arrest of WEHI-231 B lymphoma cells. J Immunol. 1988 Jun 1;140(11):3717–3726. [PubMed] [Google Scholar]
- Ransom J. T., Harris L. K., Cambier J. C. Anti-Ig induces release of inositol 1,4,5-trisphosphate, which mediates mobilization of intracellular Ca++ stores in B lymphocytes. J Immunol. 1986 Jul 15;137(2):708–714. [PubMed] [Google Scholar]
- Reth M., Hombach J., Wienands J., Campbell K. S., Chien N., Justement L. B., Cambier J. C. The B-cell antigen receptor complex. Immunol Today. 1991 Jun;12(6):196–201. doi: 10.1016/0167-5699(91)90053-V. [DOI] [PubMed] [Google Scholar]
- Rogers J., Early P., Carter C., Calame K., Bond M., Hood L., Wall R. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. Cell. 1980 Jun;20(2):303–312. doi: 10.1016/0092-8674(80)90616-9. [DOI] [PubMed] [Google Scholar]
- Runkel L., Shaw P. E., Herrera R. E., Hipskind R. A., Nordheim A. Multiple basal promoter elements determine the level of human c-fos transcription. Mol Cell Biol. 1991 Mar;11(3):1270–1280. doi: 10.1128/mcb.11.3.1270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salisbury J. L., Condeelis J. S., Satir P. Role of coated vesicles, microfilaments, and calmodulin in receptor-mediated endocytosis by cultured B lymphoblastoid cells. J Cell Biol. 1980 Oct;87(1):132–141. doi: 10.1083/jcb.87.1.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyfert V. L., Sukhatme V. P., Monroe J. G. Differential expression of a zinc finger-encoding gene in response to positive versus negative signaling through receptor immunoglobulin in murine B lymphocytes. Mol Cell Biol. 1989 May;9(5):2083–2088. doi: 10.1128/mcb.9.5.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw A. C., Mitchell R. N., Weaver Y. K., Campos-Torres J., Abbas A. K., Leder P. Mutations of immunoglobulin transmembrane and cytoplasmic domains: effects on intracellular signaling and antigen presentation. Cell. 1990 Oct 19;63(2):381–392. doi: 10.1016/0092-8674(90)90171-a. [DOI] [PubMed] [Google Scholar]
- Snow E. C., Fetherston J. D., Zimmer S. Induction of the c-myc protooncogene after antigen binding to hapten-specific B cells. J Exp Med. 1986 Sep 1;164(3):944–949. doi: 10.1084/jem.164.3.944. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vitetta E., Puré E., Isakson P., Buck L., Uhr J. The activation of murine B cells: the role of surface immunoglobulins. Immunol Rev. 1980;52:211–231. doi: 10.1111/j.1600-065x.1980.tb00336.x. [DOI] [PubMed] [Google Scholar]
- Webb C. F., Nakai C., Tucker P. W. Immunoglobulin receptor signaling depends on the carboxyl terminus but not the heavy-chain class. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1977–1981. doi: 10.1073/pnas.86.6.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson T., Treisman R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences. Nature. 1988 Nov 24;336(6197):396–399. doi: 10.1038/336396a0. [DOI] [PubMed] [Google Scholar]
- Wittner M. K., Bach M. A., Köhler H. Immune response to phosphorylcholine. IX. Characterization of hybridoma anti-TEPC15 antibodies. J Immunol. 1982 Feb;128(2):595–599. [PubMed] [Google Scholar]
- Yamanashi Y., Kakiuchi T., Mizuguchi J., Yamamoto T., Toyoshima K. Association of B cell antigen receptor with protein tyrosine kinase Lyn. Science. 1991 Jan 11;251(4990):192–194. doi: 10.1126/science.1702903. [DOI] [PubMed] [Google Scholar]