CD200 Expression in B-lineage Neoplasms

Immunophenotypic characterization of lymphoid neoplasms plays an important role in aiding the disease diagnosis, subclassification, staging, and monitoring of hematologic neoplasms.1 CD200 has recently been identified as a potentially useful antigen for flow cytometric immunophenotyping of lymphoid neoplasms, particularly those of the B lineage.2

CD200 is a type I immunoglobulin super family membrane glycoprotein, which is expressed in various mature B‐cell neoplasms (MBN).3 The expression pattern of CD200 by flow cytometry immunophenotyping can provide utility in narrowing down the differential diagnosis of MBN, particularly in low‐grade lymphomas.4 Using flow cytometric immunophenotyping, CD200 expression was found to be upregulated in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) when compared with normal B cells.5

Several previous studies have examined differential CD200 expression in B-lineage neoplasms, initially focusing on the distinction between CLL, usually brightly positive for CD200, and mantle cell lymphoma (MCL), usually CD200 negative.6 In the study by Sandes et al.,7 CD200 was expressed by all atypical CLL cases, thus being helpful for the distinction with MCL, particularly on cases with absent or dim CD23.

Brunetti et al8 showed increased CD200 expression in hairy cell leukemia (HCL). Subsequently, others using flow cytometry analysis9 have shown that CD200 is expressed at different levels in a range of B-cell neoplasms.

Figure 1. CD200 expression patterns in normal B-cell populations and B-cell neoplasms (CD200 median fluorescence intensity plotted for each case).

CD200 was moderately bright in peripheral blood (PB) B cells, bone marrow hematogones, and reactive nodal CD10– extra–follicle center (EFC) B cells, and dim in reactive nodal CD10+ follicle center (FC) B cells. CD200 was very bright in hairy cell leukemia (HCL) and moderate-to-bright in chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (LPL). CD200 expression was heterogeneous from case to case in large B-cell lymphoma (LBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). CD200 was minimally expressed in cases of Burkitt lymphoma (BL) and was dim or negative in 95% of mantle cell lymphoma (MCL) cases, with rare exceptions.1


  2. Challagundla P, Medeiros LJ, Kanagal-Shamanna R, Miranda RN, Jorgensen JL. Differential expression of CD200 in B-cell neoplasms by flow cytometry can assist in diagnosis, subclassification, and bone marrow staging. Am J Clin Pathol. 2014 Dec;142(6):837-44. doi: 10.1309/AJCPBV9ELXC0ECVL. PMID: 25389338.
  3. McCaughan GW, Clark MJ, Barclay AN. Characterization of the human homolog of the rat MRC OX-2 membrane glycoprotein. Immunogenetics. 1987;25:329-335.
  4. Rahman K, Kumar P, Gupta R, Singh MK, Nityanand S. Role of CD200 in differential diagnosis of mature B-cell neoplasm. Int J Lab Hematol. 2017 Aug;39(4):384-391. doi: 10.1111/ijlh.12637. Epub 2017 Apr 19. PMID: 28422443.
  5. McWhirter JR, Kretz-Rommel A, Saven A, et al. Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation. Proc Natl Acad Sci U S A. 2006;103:1041-1046.
  6. Palumbo GA, Parrinello N, Fargione G, et al. CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res. 2009;33:1212-1216.
  7. Sandes AF, Chauffaille M de L, M.C. Oliveira CR, Maekawa Y. Tamashiro N, Takao TT, Ritter EC, Rizzatti EG. CD200 Has an Important Role in the Differential Diagnosis of Mature B-Cell Neoplasms by Multiparameter Flow Cytometry. Cytometry Part B 2014; 86B: 98–105.
  8. Brunetti L, Di Noto R, Abate G, et al. CD200/OX2, a cell surface molecule with immuno-regulatory function, is consistently expressed on hairy cell leukaemia neoplastic cells. Br J Haematol. 2009;145:665-667.
  9. Dorfman DM, Shahsafaei A. CD200 (OX-2 membrane glycoprotein) expression in B cell–derived neoplasms. Am J Clin Pathol. 2010;134:726-733.

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