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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 1

Isolation of monoclonal VLRB MM3.

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Isolation of monoclonal VLRB MM3.
(A) BM aspirate from a patient with mu...
(A) BM aspirate from a patient with multiple myeloma was stained with VLRB MM3 containing culture supernatant from transiently transfected HEK293T cells. The cells were costained for CD38 and CD45 expression and separated into non-PCs (gate I, CD38–/lo), nonmalignant PCs (gate II, CD45+/CD38++), and malignant PCs (gate III, CD45–/lo/CD38++). Histograms depict VLRB MM3 reactivity within the indicated gates. VLRB MM3 signals are indicated by solid black lines, and negative control VLR4 signals are shown as solid gray histograms. (B) Structural characteristics of VLRB MM3. Individual VLRB MM3 units consist of a signal peptide (SP), N-terminal LRR (LRR NT), LRR-1, three variable LRRv units, a connecting peptide, C-terminal capping LRR (LRR CT), and the invariable stalk region. Location of engineered sequences encoding the HA- and 6xHis epitope tags (H/H) into the stalk region are indicated. (C) Western blot (WB) analysis of WCLs and supernatants of HEK293T cells transiently transfected with VLRB MM3 and the multimerization-deficient mutant VLRB MM3ΔC. The samples were separated by SDS-PAGE under reducing and nonreducing conditions, and recombinant VLRB protein was detected with Abs specific to the HA-epitope tag. LLR, leucine-rich repeat; PCs, plasma cells; VLRB, variable lymphocyte receptor B; WCLs, whole-cell lysates.

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