CD Markers

Topic Completed: 1 February 2014

Minor changes: 1 August 2019

Revised: 13 December 2018, last major update February 2014

Copyright: (c) 2003-2018,, Inc.

PubMed Search: CD21[title], CR2[title]

Nat Pernick, M.D.
Page views in 2019: 5,952
Page views in 2020 to date: 3,260
Cite this page: Pernick N. CD21. website. Accessed July 8th, 2020.
Definition / general
  • Receptor for Epstein Barr virus (EBV) and HHV8 (J Virol 2005;79:4651)
  • Marker of dendritic cells (also CD23 and CD35)
  • Also called CR2 (complement receptor type 2), C3d receptor and EBV receptor (OMIM #120650)
  • Note: although CD21 is the receptor for EBV, it is not necessarily expressed in EBV+ tumors
  • Forms a complex with CD19, CD81 and CD225 in the membrane of mature B cells; complex is often called the B cell coreceptor complex, because CD21 binds to antigens through attached C3d (or iC3b or C3dg) when the membrane IgM binds to the antigen, which results in a greatly enhanced response B cell response to the antigen (Wikipedia)
  • Besides EBV and HHV8, also binds to breakdown products of complement component C3 (C3d), CD23 (plays a role in IgE synthesis) and possibly gamma interferon
  • CD21/35 promotes protective immunity to Streptococcus pneumoniae through a complement-independent, but CD19-dependent pathway that regulates PD-1 expression (J Immunol 2009;183:3661)
  • Follicular dendritic cells produce a different isoform of CD21 than B cells (J Exp Med 1997;185:165)
  • Genetic CD21 deficiency is associated with hypogammaglobulinemia (J Allergy Clin Immunol 2012;129:801)
Clinical features
Uses by pathologists
Microscopic (histologic) images

Images hosted on Pathout server:

Follicular dendritic cell sarcoma


Lymph node

 Other tumors

Littoral cell
angioma of
spleen (CD21+
lining cells)


Lymph node: nodular lymphocyte
predominant Hodgkin lymphoma;
CD21 highlights follicular dendritic
cell networks within nodules

Images hosted on other servers:
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Liver (figure 2B)

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Spine (figure 3A)

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Follicular lymphoma:
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Clusters of dendritic cells in testicular tumor

  Other tumors:
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Nodal marginal zone B cell lymphoma

Positive staining - normal
  • Mature B cells (particularly marginal and mantle cells), follicular dendritic cells, pharyngeal and cervical epithelial cells, some thymocytes and some T cells
Positive staining - disease
Negative staining
  • Basophils, fibroblastic reticulum cells and related tumors, interdigitating dendritic cells and related tumors (Am J Clin Pathol 2001;115:589), Langerhans cells and related tumors, plasma cells
  • Dendritic cell neurofibroma with pseudorosettes (Am J Surg Pathol 2001;25:587)
  • Histiocytic sarcoma (Am J Surg Pathol 2004;28:1133), indeterminate cell tumors in lymph nodes
  • Inflammatory fibroid polyps of GI tract (Am J Surg Pathol 2004;28:107), inflammatory myofibroblastic tumor and splenic hamartomas
  • Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
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