CD 35

Dako (Ber-MAC-DRC, To5) and Immunotech (J3D3).

This antibody can be used on formalin-fixed, paraffin-embedded tissue section. Enzymatic digestion with proteolytic enzymes (e.g. pronase) for antigen retrieval must be performed for optimum immunoreaction. HIER enhances immunoreactivity, especially when Target Retrieval Solution is employed. The CD 35 antibody may also be applied to acetone-fixed cryostat sections or fixed-cell smears.

DAKO-CD 35 (isotype: IgG 1, k) reacts with a formalin-resistant epitope of the receptor for the C3b fragment of the third component of human complement (Gerdes et al, 1982). This receptor, which is often referred to as CR1, consists of a single glycoprotein chain with a molecular weight of approximately 220 kD. The antigen has been designated CD 35 in the system for classifying human leukocyte antigens and is therefore equivalent to To5 (Bettelheim, 1989).
In frozen sections of normal tissues, DAKO-CD 35 shows immunostaining of B-cell follicles of lymphoid tissue. The most strongly labeled cells within B-cell follicles are follicular dendritic cells (FDCs), but mantle zone lymphoid cells also immunoreact to a lesser degree. The C3b receptor on epithelial cells of renal glomeruli may also be clearly demonstrated with this antibody. Further, enzyme-treated, routinely processed paraffin sections show strong immunoreaction of FDCs in lymphoid tissue (both nodal and extranodal). The well-defined dense meshworks of FDCs in germinal centers are well demonstrated with this antibody (Fearon, 1980).

Immunohistological analyses of FDCs in paraffin sections are confined to the demonstration of FDC meshworks in reactive and neoplastic lymphoid tissue. In this regard identical immunoreactions of the dendritic cell processes of FDC are demonstrated with antibodies to both CD 21 and CD 35. Hence, the application of antibody to CD 35 in surgical pathology (being similar to CD 21) remains largely for the demonstration of FDC meshworks in follicles of HIV lymphadenopathy, Castleman disease, follicular lymphoma, follicular colonization by low-grade B-cell MALT lymphoma and nodular lymphocyte-predominant Hodgkin's disease. Demonstration of FDCs with CD 35 antibody is also useful in mantle cell lymphoma and peripheral T-cell lymphoma-AILD type (Chan, 1996). In contrast to follicular lymphomas in which the lymphomas cells are encased within a network of proliferating FDCs, the network of FDCs in mantle cell lymphoma is loosely arranged. In angioimmunoblastic T-cell lymphoma, there is a pronounced proliferation of FDCs around postcapillary venules. Finally, the application of antibody to CD 35 in the diagnosis of FDC tumors is discussed in the section on CD 21 (p 71)
Recently, another antibody to FDC has been generated. The CNA.42 antibody is reactive in fixed, paraffin-embedded sections and stains FDCs but apparently identifying an antigen different from other known anti-FDC antibodies (Raymond et al, 1997). The antibody also labels some T-cell lymphomas as well as a variety of soft tissue tumors and a proportion of carcinomas of the gastrointestinal tract and lung. The antigen is conserved in a wide spectrum of animal tissues other than human.

In postchemotherapy excision specimens, immunostaining with a CD 21/CD 35 antibody cocktail is useful to highlight dispersed small islands of residual tumor among the negative foamy histiocytes (Chan et al, 1997). Reactive germinal centers highlighted by antibodies to FDCs are ideal for use as positive control tissue.

•Bettelheim P 1989. M8, cluster report: CD 35. In: Knapp W et al, (eds). Leucocyte typing IV. White cell differentiation antigens. Oxford: Oxford University Press, 829-830.

•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.

•Fearon DT 1980. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. Journal of Experimental Medicine 152: 20-30.

•Gerdes J, Naiem M, Mason DY, Stein H 1982. Human complement (C3b) receptors defined by a mouse monoclonal antibody. Immunology 45: 645-653.

•Raymond I, Al Saati TA, Tkaczuk J et al 1997. CAN.42, a new monoclonal antibody directed against a fixative-resistant antigen of follicular dendritic reticulum cells. American Journal of Pathology 151: 1577-1585.

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