CD Markers - CD21

Home Chapter Home Jobs Conferences Fellowships Books

CD Markers

CD21

Reviewers: Nat Pernick, M.D. (see Reviewers page)
Revised: 21 January 2011, last major update January 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

General
=========================================================================

● Receptor for EBV and marker of dendritic cells

Terminology
=========================================================================

● Also called CR2 (complement receptor type 2), C3d receptor, EBV receptor

Physiology
=========================================================================

● 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)
● Binds to Epstein Barr virus (EBV) and HHV8 (J Virol 2005;79:4651)
● 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)

Clinical features
=========================================================================

● Hodgkin’s lymphoma demonstrates disruption of follicular dendritic cell-germinal cell clusters (evaluated by CD21 and CD23)
● Note: although CD21 is the receptor for EBV, it is not necessarily expressed in EBV+ tumors
● Shows variability in flow cytometry expression between specimens from same patient (Am J Clin Pathol 2002;117:615)
● Genetic variations are associated with susceptibility to systemic lupus erythematosus (MIM 610927)
● For soluble serum CD21, levels in patients with limited cutaneous systemic sclerosis < levels in patients with diffuse cutaneous systemic sclerosis < normal patients (Rheumatol Int 2010 Oct 30 [Epub ahead of print])

Uses
=========================================================================

● 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’s 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)

Micro images
=========================================================================

Normal germinal center

Follicular dendritic cell sarcoma:

Liver (figure 2B) Spine (figure 3A)

Figure 1: liver tumor (inset: splenic tumor); 2a/b: H&E; 2c: CD21; 2d: CD35

Follicular lymphoma:

Well organized clusters of dendritic cells in testicular tumor

Head and neck tumors

Other tumors:

Nodal marginal zone B cell lymphoma

Peripheral T cell lymphoma resembling follicular lymphoma

Littoral cell angioma of spleen (CD21+ lining cells)

Positive staining - normal
=========================================================================

● Mature B cells (particularly marginal and mantle cells), follicular dendritic cells, pharyngeal and cervical epithelial cells, some thymocytes, 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's disease (Am J Surg Pathol 2002;26:662), splenic littoral cell angiomas (lining cells are CD21+, Am J Surg Pathol 1997;21:827), 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, splenic hamartomas
● Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Additional references
=========================================================================

● MIM 120650

End of CD Markers > CD21

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).