CD Markers
CD21

Author: Nat Pernick, M.D. (see Authors page)

Revised: 21 December 2015, last major update February 2014

Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

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

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
Pathophysiology
  • 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
Micro Images

Follicular dendritic cell sarcoma:

Images hosted on Pathout server:

Duodenum

Lymph node



Images hosted on other servers:

Liver (figure 2B)

Mediastinum

Oral cavity (figure A)

Spine (figure 3A)

Tonsil


Follicular lymphoma:

Well organized clusters of dendritic cells in testicular tumor (fig C)



Other tumors:

Images hosted on Pathout server:

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:

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)