CD 21

Dako (1F8), Coulter (B2) and Immunotech (BL13).

CD 21 is applicable to formalin-fixed, paraffin-embedded tissue sections. Enzymatic digestion with proteolytic enzyme trypsin is essential for positive immunoreaction but HIER produces significant enhancement of immunoreactivity. CD 21 may also be used for labeling acetone-fixed cryostat sections or fixed-cell smears.

CD 21 antigen (CR2) (Isotype: IgG1 k) represents the purified receptor of the C3d fragment of the third complement component from human tonsils (Weiss et al, 1984). This membrane molecule is a glycoprotein of molecullar weight of 145 kD and is involved in the transmission of growth-promoting signals to the interior of the B cell. CD 21 also functions as a receptor for Epstein-Barr virus (Nemerow et al, 1985). IF8 reacts with an epitope localized on trypsin fragments of CR2 of molecular weights 95,72,50,32 and 28 kD (Mason et al, 1986). The 28kD and 72 kD molecular weight fragments of CR2 contains the binding site for the C3d receptor.
The CD 21 antigen is a restricted B-cell antigen expressed on mature B cells. The antigen is also present on follicular dendritic cells (FDCs), the accessory cells of the B zones. IF8 labels B cells moderately and demonstrates FDCs strongly on cryostat sections. However, on paraffin sections, B-cell immunoreaction is abolished whilst the FDCs remain highlighted, similar to the cryostat sections. Hence, in normal and reactive lymph nodes, tonsils and extranodal lymphoid tissue, the antibody demonstrates the FDC meshwork remarkably clearly defined in the germinal centers (Mason et al, 1986).

On paraffin sections, antibodies to the CD 21 antigen are useful to demonstrate FDC meshwork in lymphoid proliferations where the germinal centers may be illdefined and difficult to delineate morphologically, e.g. HIV lymphadenopathy. In the early stages of progressive generalized lymphadenopathy (PGL, stage I), the large geographic reactive germinal centers may occupy large areas of the lymph node, giving an appearance of effacement of the architecture. Similarly, in the late stage of PGL (stage III), the atrophic germinal centers are not easily definable.
The demonstration of the nodular dense FDC meshwork of follicular lymphomas is also a potential application of the CD 21 antibody. Similarly, the follicular/nodular architecture of nodular lymphocyte-predominant Hodgkin's disease may be highlighted. Residual germinal centers that have been colonized in low-grade B-cell MALT lymphomas may also be demonstrated with antibody to CD 21 which reveals the FDC meshwork. Nodal mantle cell lymphoma and multiple lymphomatous polyposis are characterized by the presence of monotonous small lymphoid B-cell population and interspersed cells with ''naked" nuclei (FDCs), which is helpful in distinguishing this lymphoma from other low-grade B-cell lymphomas (Chan, 1996). The demonstration of a FDC meshwork is also characteristic of peripheral T-cell lymphomas of angioimmunoblastic lymphadenopathy (AILD) type. The FDC meshwork in AILD is typically around hyperplastic venules.
The diagnosis of angiofollicular lymph node hyperplasia or Castleman's disease (hyaline-vascular type) may also benefit from highlighting the follicles with anti-CD 21. Dysplastic FDCs have been demonstrated in association with Castleman's disease and are thought to be the precursor to FDC tumors. Again, the characteristic dendritic processes in FDC tumors are well demonstrated with CD 21 antibodies (Chan et al, 1997).

Although sometimes patchy and focal, reactivity with the paraffin section-reactive CD 21 is essential for the diagnosis of FDC tumors which are probably underdiagnosed through underrecognition.

•Chan JKC 1996. Gastrointestinal lymphomas: an overview with emphasis on new findings and diagnostic problems. Seminars in Diagnostic Pathology 13: 260-296.

•Chan JKC, Fletcher CDM, Nayler SJ, Cooper K 1997. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer 79: 294-313.

•Mason DY, Ladyman H, Gatter KC 1986. Immunohistochemical analysis of monoclonal anti-B cell antibodies. In: Reinherz EL, Haynes BF, Nadler LM, Bernstein ID, (eds). Leukocyte Typing II, Volume 2. Human B lymphocytes. New York - Berlin - Heidelberg - Tokyo: Springer-Verlag, pp 245-255.

•Nemerow GR, Wolfert R, McNaughton ME, Cooper NR 1985. Identification and characterization of the Epstein-Barr virus receptor on human B lymphocytes and its relationship to the C3D complement receptor (CR2). Journal of Virology 55: 347-351.

•Weiss JJ, Tedder TF, Fearon DT 1984. Identification of 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. Proceedings of the National Academy of Science USA 81: 881-885.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.