CD Markers
CD21
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CD21, CR2
CD21
Author: Nat Pernick, M.D.
Last author update: 1 February 2014
Last staff update: 18 August 2023
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CD21, CR2
Table of Contents
Definition / general | Pathophysiology | Clinical features | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative stainingCite this page: Pernick N. CD21. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd21.html. Accessed December 16th, 2024.
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
- Variable expression by flow cytometry in specimens from same patient (Am J Clin Pathol 2002;117:615)
- Hodgkin lymphoma: disruption of follicular dendritic cell-germinal cell clusters can be evaluated by CD21 and CD23
- Genetic variations are associated with susceptibility to:
- nasopharyngeal carcinoma (Oncol Rep 2013;30:11)
- systemic lupus erythematosus (Proc Natl Acad Sci USA 2007;104:3961, OMIM #610927)
Uses by pathologists
- CD21, CD23 and CD35 are dendritic cell markers
- Diagnosis of follicular dendritic cell sarcomas (Am J Surg Pathol 1996;20:944)
- Assess follicular dendritic cell meshwork infrastructure (Am J Clin Pathol 2005;124:182, Am J Surg Pathol 2001;25:388)
- Distinguish cutaneous or nodal marginal zone lymphoma from follicular lymphoma (Am J Surg Pathol 2001;25:732, Int J Surg Pathol 2005;13:73)
- Distinguish splenic littoral cell angioma (CD21+ lining cells) from splenic hamartomas (CD21-, Am J Surg Pathol 1997;21:827)
- Confirm that atypical cells have follicular dendritic origin in fine needle aspirates of hyaline-vascular Castleman disease (Diagn Cytopathol 2000;22:230)
- Differentiate invasive Quilty lesions (central aggregate of B cells with a rim of T cells admixed with capillary vessels) from cardiac acute cellular rejection (Am J Surg Pathol 2006;30:1008)
Microscopic (histologic) images
AFIP images and Cases #81, 179 and 284
Follicular dendritic cell sarcoma
Littoral cell angioma of spleen
Lymph node
Images hosted on other servers:
Mediastinum
Tonsil
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
- Follicular dendritic cell tumor (Am J Surg Pathol 2004;28:988, Am J Surg Pathol 2001;25:721), hairy cell leukemia, B cell lymphomas (particularly mantle and marginal zone), hyaline vascular variant of Castleman disease (Am J Surg Pathol 2002;26:662), splenic littoral cell angiomas (lining cells are CD21+, Am J Surg Pathol 1997;21:827) and some T-ALL
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)
