Long-Lived Plasma Cells Are Contained within the CD19-CD38hiCD138+ Subset in Human Bone Marrow

被引：378

作者：

Halliley, Jessica L. ^{[1
,2
,3
,4
]}

Tipton, Christopher M. ^{[5
,6
,7
]}

Liesveld, Jane ^{[8
,9
]}

Rosenberg, Alexander F. ^{[10
]}

Darce, Jaime ^{[11
]}

Gregoretti, Ivan V. ^{[11
]}

Popova, Lana ^{[11
]}

Kaminiski, Denise ^{[10
]}

Fucile, Christopher F. ^{[10
]}

Albizua, Igor ^{[1
,2
,3
]}

Kyu, Shuya ^{[1
,2
,3
]}

Chiang, Kuang-Yueh ^{[12
]}

Bradley, Kyle T. ^{[13
]}

Burack, Richard ^{[14
]}

Slifka, Mark ^{[15
]}

Hammarlund, Erika ^{[15
]}

Wu, Hao ^{[16
]}

Zhao, Liping ^{[16
]}

Walsh, Edward E. ^{[17
,18
]}

Falsey, Ann R. ^{[17
,18
]}

Randall, Troy D. ^{[19
]}

Cheung, Wan Cheung ^{[11
]}

Sanz, Inaki ^{[5
,6
,7
]}

Lee, F. Eun-Hyung ^{[1
,2
,3
,6
,7
]}

机构：

[1] Emory Univ, Div Pulm, Atlanta, GA 30322 USA

[2] Emory Univ, Div Allergy, Atlanta, GA 30322 USA

[3] Emory Univ, Div Crit Care Med, Atlanta, GA 30322 USA

[4] Univ Rochester, Med Ctr, Pulm & Crit Care Med, Rochester, NY 14642 USA

[5] Emory Univ, Div Rheumatol, Atlanta, GA 30322 USA

[6] Emory Univ, Lowance Ctr Human Immunol, Dept Med, Atlanta, GA 30322 USA

[7] Emory Univ, Lowance Ctr Human Immunol, Dept Pediat, Atlanta, GA 30322 USA

[8] Univ Rochester, Med Ctr, Div Hematol, James P Wilmot Canc Inst, Rochester, NY 14642 USA

[9] Univ Rochester, Med Ctr, Div Oncol, James P Wilmot Canc Inst, Rochester, NY 14642 USA

[10] Univ Rochester, Med Ctr, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA

[11] Cell Signaling Technol Inc, Danvers, MA 01923 USA

[12] Emory Univ, Dept Pediat, Aflac Canc & Blood Disorders Ctr, Atlanta, GA 30322 USA

[13] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[14] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA

[15] Oregon Hlth & Sci Univ, Beaverton, OR 97006 USA

[16] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

[17] Univ Rochester, Med Ctr, Div Infect Dis, Rochester, NY 14621 USA

[18] Rochester Gen Hosp, Rochester, NY 14621 USA

[19] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA

来源：

IMMUNITY | 2015年 / 43卷 / 01期

关键词：

MEMORY B-CELLS; HUMAN MONOCLONAL-ANTIBODIES; HUMORAL IMMUNITY; SECRETING CELLS; BLOOD; SURVIVAL; EXPRESSION; CLONING; DIFFERENTIATION; RESPONSIVENESS;

D O I：

10.1016/j.immuni.2015.06.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM). We found that the CD19(-)CD38(hi)CD138(+) subset was morphologically distinct, differentially expressed PC-associated genes, and exclusively contained PCs specific for viral antigens to which the subjects had not been exposed for more than 40 years. Protein sequences of measles-and mumps-specific circulating antibodies were encoded for by CD19(-)CD38(hi)CD138(+) PCs in the BM. Finally, we found that CD19(-)CD38(hi)CD138(+) PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and probably represents the B cell response's "historical record'' of antigenic exposure. Thus, our studies define human LLPCs and provide a mechanism for the life-long maintenance of anti-viral antibodies in the serum.

引用

页码：132 / 145

页数：14

共 48 条

[1] Maintenance of the plasma cell pool is independent of memory B cells [J].