TY - JOUR
T1 - CD138 mediates selection of mature plasma cells by regulating their survival
AU - McCarron, Mark J.
AU - Park, Pyong Woo
AU - Fooksman, David R.
N1 - Funding Information:
This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (AI072529) (D.R.F.), and the core facilities were supported by the Albert Einstein Cancer Center. M.J.M. was supported by The Philippe Foundation.
PY - 2017/5/18
Y1 - 2017/5/18
N2 - 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.
AB - 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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U2 - 10.1182/blood-2017-01-761643
DO - 10.1182/blood-2017-01-761643
M3 - Article
C2 - 28381397
AN - SCOPUS:85019726515
VL - 129
SP - 2749
EP - 2759
JO - Blood
JF - Blood
SN - 0006-4971
IS - 20
ER -