TY - JOUR
T1 - Evidence for B cell exhaustion in chronic graft-versus-host disease
AU - Khoder, Ahmad
AU - Alsuliman, Abdullah
AU - Basar, Rafet
AU - Sobieski, Catherine
AU - Kondo, Kayo
AU - Alousi, Amin Majid
AU - Szydlo, Richard
AU - Muftuoglu, Muharrem
AU - Shaim, Hila
AU - Apperley, Jane F.
AU - Gokdemir, Elif
AU - Cooper, Nichola
AU - Mehta, Rohtesh S.
AU - Marin, David
AU - Champlin, Richard
AU - Shpall, Elizabeth
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2018 Khoder, Alsuliman, Basar, Sobieski, Kondo, Alousi, Szydlo, Muftuoglu, Shaim, Apperley, Gokdemir, Cooper, Mehta, Marin, Champlin, Shpall and Rezvani.
PY - 2018/1/12
Y1 - 2018/1/12
N2 - Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21- B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21- B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27-CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21- B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21- B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21- B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21-CD27-CD10- B cell frequencies as a biomarker of disease severity.
AB - Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21- B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21- B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27-CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21- B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21- B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21- B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21-CD27-CD10- B cell frequencies as a biomarker of disease severity.
KW - CD19+CD21-CD27-CD10- cells
KW - CD21- B cells correlate with cGVHD severity
KW - Chronic graft-versus-host disease
KW - Exhausted B cells
KW - Stem cell transplantation
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U2 - 10.3389/fimmu.2017.01937
DO - 10.3389/fimmu.2017.01937
M3 - Article
C2 - 29375566
AN - SCOPUS:85040525854
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JAN
M1 - 1937
ER -