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Identification of human plasma cells with a lamprey monoclonal antibody
Cuiling Yu, … , Max D. Cooper, Götz R.A. Ehrhardt
Cuiling Yu, … , Max D. Cooper, Götz R.A. Ehrhardt
Published March 17, 2016
Citation Information: JCI Insight. 2016;1(3):e84738. https://doi.org/10.1172/jci.insight.84738.
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Resource and Technical Advance Immunology

Identification of human plasma cells with a lamprey monoclonal antibody

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Abstract

Ab-producing plasma cells (PCs) serve as key participants in countering pathogenic challenges as well as being contributors to autoimmune and malignant disorders. Thus far, only a limited number of PC–specific markers have been identified. The characterization of the unique variable lymphocyte receptor (VLR) Abs that are made by evolutionarily distant jawless vertebrates prompted us to investigate whether VLR Abs could detect novel PC antigens that have not been recognized by conventional Abs. Here, we describe a monoclonal lamprey Ab, VLRB MM3, that was raised against primary multiple myeloma cells. VLRB MM3 recognizes a unique epitope of the CD38 ectoenzyme that is present on plasmablasts and PCs from healthy individuals and on most, but not all, multiple myelomas. Binding by the VLRB MM3 Ab coincides with CD38 dimerization and NAD glycohydrolase activity. Our data demonstrate that the lamprey VLRB MM3 Ab is a unique reagent for the identification of plasmablasts and PCs, with potential applications in the diagnosis and therapeutic intervention of PC or autoimmune disorders.

Authors

Cuiling Yu, Yanling Liu, Justin Tze Ho Chan, Jiefei Tong, Zhihua Li, Mengyao Shi, Dariush Davani, Marion Parsons, Srijit Khan, Wei Zhan, Shuya Kyu, Eyal Grunebaum, Paolo Campisi, Evan J. Propst, David L. Jaye, Suzanne Trudel, Michael F. Moran, Mario Ostrowski, Brantley R. Herrin, F. Eun-Hyung Lee, Ignacio Sanz, Max D. Cooper, Götz R.A. Ehrhardt

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Figure 2

PC specificity of VLRB MM3.

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PC specificity of VLRB MM3.
(A) Human tonsillar lymphocytes were separat...
(A) Human tonsillar lymphocytes were separated into the following subpopulations: IgD– PCs (CD19+/IgD–/CD38++); IgD+ PCs (CD19+/IgD+/CD38++); naive B cells (CD19+/IgD+/CD38–); memory B cells (CD19+/IgD–/CD38–); pregerminal center B cells (CD19+/IgD+/CD38+); germinal center B cells (CD19+/IgD–/CD38+); non–B/T cells (CD19–/CD3–); and T cells (CD19–/CD3+). Shown is a representative of 15 examined tonsil tissues. Human splenic cells were separated into the indicated cell subpopulations described for tonsillar cells, with non–B cells encompassing all CD19– cells. Human BM was separated into PCs (CD38++/CD138+) and non-PCs (CD38–/CD138–). Shown is a representative of 3 analyzed BM tissue samples. Note that the BM sample was stained with Fc-MM3 fusion proteins. Human PBMCs were separated into naive B cells (CD19+/IgD+/CD27–), memory B cells (CD19+/IgD–/CD27+), marginal zone equivalent cells (CD19+/IgD+/CD27+), transitional B cells (CD19+/IgD+/CD27–/CD10+/CD24+), non–B/T cells (CD19–/CD3–), T cells (CD19–/CD3+), and monocytes (FSC/SSC characteristics). Shown is a representative example of 6 PBMC samples. Plasmablasts from influenza vaccine–immunized individuals were identified as CD19+/CD3–/IgD–/CD38++/CD27+. Shown is a representative example of 8 analyzed blood samples from day 7 after vaccination. VLRB MM3 signals are indicated by solid black lines and negative control VLR4 signals are shown as solid gray histograms. (B) NHP BM samples were stained with VLRB MM3 and gated on the lymphocyte gate (FSC/SSC). VLRB MM3–positive cells were FACS purified and analyzed by transmission electron microscopy (original magnification, ×4,000). Scale bar: 1 μm. In all histograms, VLRB MM3 reactivity is indicated by solid black lines, and negative control VLR4 signals are indicated by filled gray histograms. FSC/SSC, forward scatter/side scatter; GC, germinal center; NHP, nonhuman primate; Non-B, non–B cells; PBMCs, peripheral blood mononuclear cells; PCs, plasma cells; T, T cells; VLRB, variable lymphocyte receptor B.

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