CD23

Synonyms: low affinity IgE receptor, Leu-20, FcεRII

by Assia Bassarova

Background

CD23 is a type II integral membrane single chain glycoprotein with molecular weight of 45 kDa. Two subtypes, FcεRIIa/CD23a and FcεRIIb/CD23b, have been identified. They differ in tissue-specific gene expression and regulation. FcεRIIa is believed to be constitutively expressed only in normal B-cells, B-cell lines (perhaps follicular dendritic cells), and eosinophils, whereas FcεRII b is induced in various cell types. The human FcεRII/CD23 gene has been mapped to chromosome 19p13.3. CD23 is the only FcR which does not belong to the immunoglobulin gene superfamily. CD23 may exist on cell membranes as a dimer or trimer. It also exists as a soluble excreted form that display autocrine promoting activity. CD23 appears to mediate various forms of IgE-mediated immunity. Expression of CD23 on blood lymphocytes, alveolar macrophages, airway smooth muscle cells, and even serum soluble CD23 have been linked to allergic diseases. CD23 is a B-cell-specific antigen and it has essential roles in the regulation of IgE production and in the differentiation of B-cells. In the B cell compartment, sCD23 sustains the growth of activated mature B lymphocytes, possibly via an autocrine mechanism, promotes differentiation of germinal center centroblasts towards the plasma cell pool [in association with interleukin (IL)-1α, and allows B cell precursors to evade apoptosis. In other lineages, sCD23 promotes differentiation of myeloid precursors, thymocytes and bone marrow CD4+ T cells, again in association with IL-1α, and also drives cytokine release by monocytic cells. CD23 is upregulated in Eppstein-Barr infection. CD23 is constitutively expressed by intestinal epithelial cells and its expression is enhanced in enteropathies.

Staining in normal cells/tissues

It is widely distributed in various human cells, including B-cells, monocytes and macrophages, eosinophils, platelets, epidermal Langerhans’ cells, follicular dendritic cells, keratocytes, and even airway smooth muscle cells.

Staining in tumors

Many reports suggest that elevated CD23, either on neoplastic cell surfaces or as a soluble form, is a useful marker in either diagnosis or prognosis of disease. CD23 is typically expressed in chronic lymphocytic leukemia (CLL), sometimes in follicular lymphoma, rarely in marginal zone and lymphoplasmacytic lymphoma. Some recent reports have shown low CD23 expression even in mantle cell lymphoma. In CLL, the strongest expression is characteristically present in proliferation centers. It was recently demonstrated that patients with CD23-positive diffuse large B-cell lymphoma have good prognosis. CD23 is also frequently used to demonstrate benign follicular dendritic cells in the background of follicular lymphoma, marginal zone lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, follicular T-cell lymphoma. Together with CD21, CD23 is a marker of rare follicular dendritic cell tumors.

Staining pattern

Strong membranous staining in the follicular dendritic cells and at least weak to moderate staining in the activated B-cells of the mantle zones.

Control tissue

Appendix / tonsil is recommended tissue control for CD23. The follicular dendritic cells of the germinal centers must be stained as strongly as possible. In the mantle zone, the activated B-cells must show an at least weak to moderate and distinct continuous membranous staining reaction. The T-cell areas and squamous / glandular epithelial cells must be completely negative.

Application

  • In diagnostic pathology CD23 is primarily used in the panel for small B-cell lymphoproliferative disorders.

Selected references

  1. Acharya M, Borland G, Edkins AL, et al. CD23/FcεRII: molecular multi-tasking. Clin Exp Immunol. 2010 Oct;162(1): 12-23. doi: 10.1111/j.1365-2249.2010.04210.x. PMID: 20831712; PMCID: PMC2990925.
  2. Bonnefoy J-Y, Lecoanet-Henchoz S, Gauchat J-F, et al. Structure and Functions of CD23. International Reviews of Immunology 1997; 16(1-2), 113–128. doi:10.3109/08830189709045705
  3. Gars E, Butzmann A, Ohgami R, et al. The life and death of the germinal center. Ann Diagn Pathol. 2020 Feb; 44:151421. doi: 10.1016/j.anndiagpath.2019.151421. Epub 2019 Nov 13. PMID: 31751845.
  4. Rosenwasser LJ, Meng, J. Anti-CD23. Clinical Reviews in Allergy & Immunology, 2005; 29(1), 061–072. doi:10.1385/criai:29:1:061
  5. Saksena A, Yin CC, Xu J, et al. CD23 expression in mantle cell lymphoma is associated with CD200 expression, leukemic non-nodal form, and a better prognosis. Hum Pathol. 2019 Jul; 89:71-80. doi: 10.1016/j.humpath.2019.04.010. Epub 2019 May 2. PMID: 31054894.
  6. Yoshino T, Tanaka T, Sato Y. Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma. J Clin Exp Hematop. 2020 Dec 15;60(4):124-129. doi: 10.3960/jslrt.19041. Epub 2020 Apr 3. PMID: 32249238; PMCID: PMC7810253.