CD 5

Ancell (UCHT2), Becton Dickinson (Leu1), Biodesign (BL1a, UCHT2), Biogenex (T1), Bioprobe (T1), Coulter (T1), Cymbus Bioscience (UCHT2), Dako (DK23), GenTrak, Immunotech (BL1a), Oncogene (UCHT2), Sanbio (BL-TP), Seralab (UCHT2), Serotec, Sigma and Pharmingen (UCHT2).

Fresh or frozen tissue.

The CD 5 molecule is a transmembrane glycoprotein of 67 kD, with the typical tripartite structure of a signal peptide. The human CD 5 has a sequence similar to that of the Ly-1 antigen in mouse and both are distantly related members of the immunoglobulin superfamily of genes. CD 5 is expressed on both T and some B lymphocytes. It is weakly positive in the most immature T-cell precursors which are CD 34+, with the intensity of expression increasing with maturation. CD 5 expression is first seen in intrathymic T-cell progenitors (CD 5+/CD 34+) which differentiate into CD 3+/CD 4+/CD 8+ T-cells. This antigen is expressed in the majority of T-cells with only about 11% of CD 4+ lymphocytes being CD 5-. Two-thirds of these CD5-negative cells areab T-cell receptor-positive cells and one-third aregd T-cells. Anti-CD 5 antibodies have been shown to prolong the proliferative response of anti-CD 3 activated T lymphocytes by enhancing signal transduction by the T-cell receptor antigen, a process associated with increased IL-2 production and increased IL-2 receptor expression by the T-cells. The CD 5 antigen may also act as a signal-transducing molecule in a manner independent of CD 3. It has also been suggested that the B-cell surface protein CD 72 (Lyb-2) is the ligand or counterstructure for CD 5 and occupancy of CD 72 by anti-CD 72 antibodies, and possibly CD 5+ T-cells, enhances IL-4-dependent CD 23 expression on resting B- ymphocytes.
When CD 5 is expressed on B lymphocytes, it is usually weakly staining compared to the strong expression of mature T lymphocytes. This weak expression makes precise identification of the CD 5+ and CD 5- B-cell populations difficult. CD 5+ B cells (B-1 cells) are first seen in the peritoneal and pleural cavities of the fetus at gestation week 15. The cells become prominent in the fetal spleen with 60% or more of splenic B cells expressing the antigen. At birth, about 68% of cord blood B cells and approximately half of the peripheral blood B lymphocytes are CD 5+ and this level drops dramatically in the peripheral blood to near adult levels within the first year of life. Fifteen to twenty-five percent of peripheral blood B lymphocytes in adults are positive for CD 5.
There is some suggestion that CD 5+ B lymphocytes represent a distinct subpopulation. Although both CD 5+ and CD 5- B cells produce immunoglobulin, upon activation CD 5+ cells selectively produce primarily IgM antibodies, while CD 5- B cells make primarily IgG antibodies, an observation made in cord blood. CD 5+ B cells have also been reported to be associated with usually low affinity, polyreactive antibody production, often called autoantibodies. About 50% of autoantibody-associated crossreactive idiotype-bearing B lymphocytes are CD 5+. It is possible that some of these differences may be due to lineage differences or are simply secondary to some type of B-cell activation and require further investigation (Arber & Weiss, 1995).

CD 5 is a fairly specific and sensitive marker of T-cell lineage. Almost 85% of T-cell acute lymphoblastic leukemias are CD 5+ and lack of CD 5 expression in T-ALL in patients with a white cell count of less than 50 000/ml is reported to be associated with a worse prognosis than corresponding patients with CD 5+ T-cells. CD 5 expression has been reported in 3-10% of cases of acute myeloid leukemia. As CD 5 is a pan-T-cell marker, it is not surprising that the majority of T-cell malignancies (76%) are CD 5+ (Shuster et al, 1990). In peripheral T-cell lymphomas including cutaneous T-cell lymphomas, the loss of CD 5 expression can be employed to support a diagnosis of malignancy. In cutaneous T-cell lymphoma, CD 5 is not as frequently lost when compared to loss of CD 7.
With B-cell neoplasms, CD 5 expression has been considered an almost defining characteristic of many entities. Chronic lymphocytic leukemia (CLL) is the most common CD 5+ B cell malignancy. It is assumed that the small population of CD 5+ B cells found in normal healthy adults and prominent in cord blood is the non-neoplastic counterpart of this type of CLL. B-cell CLL is also associated with polyspecific antibodies or autoantibodies and frequently expresses crossreactive idiotypes. Over 90% of cases of typical CLL are CD 5+. CD 5 expression may be lost when the large cell lymphoma of Richter's syndrome supervenes in CD 5+ CLL (Matutes & Catovsky, 1991).
With rare exceptions, monocytoid B-cell lymphoma and low-grade B-cell lymphoma of mucosa-associated lymphoid tissue are usually CD 5-, a feature which can be employed to distinguish these disorders. CD 5+ B-cells have been reported to be increased in some patients with monoclonal gammopathy of undetermined significance and in cases of multiple myeloma.
CD 5 positivity has been found in cases of thymic carcinomas and some cases of atypical thymomas but not in typical thymomas (Hishima et al, 1994). Carcinomas of the lung, breast, esophagus, stomach, colon and uterine cervix have been reported to be all CD 5-.

We employ clone Leu1 in our laboratory and although most publications indicate that the CD 5 antigen is only demonstrable in fresh and frozen tissues, we have successfully demonstrated CD 5 using Leu1 antibody following MW epitope retrieval with TUR (Leong et al, 1996). A recently produced antibody to CD5 (clone NCL-CD5, Vector Laboratories) was claimed to be immunoreactive in paraffin-embedded tissues following steam heat-induced epitope retrieval but in a study of 12 CD 5+ malignancies, only one, a small cell lymphoma, was positive in fixed tissues (Ben-Ezra & Kornstein, 1996).

•Arber DA, Weiss LM 1995. CD5.A review. Applied Immunohistochemistry 3: 1-22.

•Ben-Ezra JM, Kornstein MJ 1996. Antibody NCL-CD5 fails to detect neoplastic CD5+ cells in paraffin sections. American Journal of Clinical Pathology 106:370-373.

•Hishima T, Fukayama M, Fujisawa M et al 1994. CD5 expression in thymic carcinoma. American Journal of Pathology 145: 268-75.

•Leong AS-Y, Milios J, Leong FJ 1996. Epitope retrieval with microwaves. A comparison of citrate buffer and EDTA with three commercial retrieval solutions. Applied Immunohistochemistry 4: 201-207.

•Matutes E, Catovsky D 1991. Mature T-cell leukaemias and leukaemia/lymphoma syndromes. Review of our experience in 175 cases. Leukaemia and Lymphoma 4: 81-91.

•Shuster JJ, Falletta JM, Pullen J et al 1990. Prognostic factors in childhood T-cell acute lymphoblastic leukaemia: a paediatric oncology group study. Blood 95: 116-173.

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