CD138 Mediates Selection of Mature Plasma Cells by Regulating Their Survival

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2017 Apr 7

PMID 28381397

Citations 60

Authors

Mark J McCarron

Pyong Woo Park

David R Fooksman

Affiliations

Soon will be listed here.

Abstract

Antibody secreting cells (ASCs) are critical effector cells and long-lived sentinels for immune memory. ASCs are highly dependent on exogenous soluble factors such as interleukin-6 (IL-6) and APRIL, to prevent their cell death. We have found that the canonical surface marker of ASCs, CD138 (syndecan-1), which is upregulated during ASC maturation, is required in a cell-intrinsic manner to mount an effective long-term humoral immune response following immunization. Surface expression of CD138 increased heparan sulfate levels on ASCs, which are known to bind pro-survival cytokines, leading to increased survival in a cell-intrinsic manner in vivo. In IL-6 and APRIL-deficient hosts, ASCs underwent extensive apoptosis independently of CD138 expression. We propose a model in which CD138 expression on fully mature ASCs provides a selective survival advantage over less mature, newly minted ASCs, by enhancing pro-survival cytokine signaling.

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References

Ramani V, Pruett P, Thompson C, DeLucas L, Sanderson R . Heparan sulfate chains of syndecan-1 regulate ectodomain shedding. J Biol Chem. 2012; 287(13):9952-9961. PMC: 3322978. DOI: 10.1074/jbc.M111.330803. View

Alexander C, REICHSMAN F, Hinkes M, Lincecum J, Becker K, Cumberledge S . Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nat Genet. 2000; 25(3):329-32. DOI: 10.1038/77108. View

Barbouri D, Afratis N, Gialeli C, Vynios D, Theocharis A, Karamanos N . Syndecans as modulators and potential pharmacological targets in cancer progression. Front Oncol. 2014; 4:4. PMC: 3910246. DOI: 10.3389/fonc.2014.00004. View

William J, Euler C, Shlomchik M . Short-lived plasmablasts dominate the early spontaneous rheumatoid factor response: differentiation pathways, hypermutating cell types, and affinity maturation outside the germinal center. J Immunol. 2005; 174(11):6879-87. DOI: 10.4049/jimmunol.174.11.6879. View

Roederer M, Nussenzweig M . Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol. 2002; 3(4):399-406. DOI: 10.1038/ni776. View

Kallies A, Hasbold J, Tarlinton D, Dietrich W, Corcoran L, Hodgkin P . Plasma cell ontogeny defined by quantitative changes in blimp-1 expression. J Exp Med. 2004; 200(8):967-77. PMC: 2211847. DOI: 10.1084/jem.20040973. View

Freissler E, Meyer auf der Heyde A, David G, Meyer T, Dehio C . Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells. Cell Microbiol. 2001; 2(1):69-82. DOI: 10.1046/j.1462-5822.2000.00036.x. View

Park P, Reizes O, Bernfield M . Cell surface heparan sulfate proteoglycans: selective regulators of ligand-receptor encounters. J Biol Chem. 2000; 275(39):29923-6. DOI: 10.1074/jbc.R000008200. View

Stewart M, Ramani V, Sanderson R . Shed syndecan-1 translocates to the nucleus of cells delivering growth factors and inhibiting histone acetylation: a novel mechanism of tumor-host cross-talk. J Biol Chem. 2014; 290(2):941-9. PMC: 4294521. DOI: 10.1074/jbc.M114.608455. View

10.

Jego G, Bataille R, Pellat-Deceunynck C . Interleukin-6 is a growth factor for nonmalignant human plasmablasts. Blood. 2001; 97(6):1817-22. DOI: 10.1182/blood.v97.6.1817. View

11.

Teng Y, Aquino R, Park P . Molecular functions of syndecan-1 in disease. Matrix Biol. 2011; 31(1):3-16. PMC: 3568394. DOI: 10.1016/j.matbio.2011.10.001. View

12.

Beauvais D, Ell B, McWhorter A, Rapraeger A . Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. J Exp Med. 2009; 206(3):691-705. PMC: 2699122. DOI: 10.1084/jem.20081278. View

13.

Casu B, Naggi A, Torri G . Heparin-derived heparan sulfate mimics to modulate heparan sulfate-protein interaction in inflammation and cancer. Matrix Biol. 2010; 29(6):442-52. PMC: 3057403. DOI: 10.1016/j.matbio.2010.04.003. View

14.

Chu V, Beller A, Nguyen T, Steinhauser G, Berek C . The long-term survival of plasma cells. Scand J Immunol. 2011; 73(6):508-11. DOI: 10.1111/j.1365-3083.2011.02544.x. View

15.

Beauvais D, Jung O, Yang Y, Sanderson R, Rapraeger A . Syndecan-1 (CD138) Suppresses Apoptosis in Multiple Myeloma by Activating IGF1 Receptor: Prevention by SynstatinIGF1R Inhibits Tumor Growth. Cancer Res. 2016; 76(17):4981-93. PMC: 5010496. DOI: 10.1158/0008-5472.CAN-16-0232. View

16.

Bernfield M, Gotte M, Park P, Reizes O, Fitzgerald M, Lincecum J . Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 2000; 68:729-77. DOI: 10.1146/annurev.biochem.68.1.729. View

17.

Yang Y, MacLeod V, Dai Y, Khotskaya-Sample Y, Shriver Z, Venkataraman G . The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy. Blood. 2007; 110(6):2041-8. PMC: 1976367. DOI: 10.1182/blood-2007-04-082495. View

18.

Mohr E, Serre K, Manz R, Cunningham A, Khan M, Hardie D . Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature. J Immunol. 2009; 182(4):2113-23. DOI: 10.4049/jimmunol.0802771. View

19.

Seidel C, Sundan A, Hjorth M, Turesson I, Dahl I, Abildgaard N . Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood. 2000; 95(2):388-92. View

20.

Saunders S, Jalkanen M, OFarrell S, Bernfield M . Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol. 1989; 108(4):1547-56. PMC: 2115498. DOI: 10.1083/jcb.108.4.1547. View