CD 38

Sources/Clones
Accurate (BCAP38), Advanced Immunochemical (24G3), Biodesign (MIG-P12, T16), Biosource (BA6), Caltag Laboratories (BL-AC38, HIT2), Coulter (CD 38, T16), Cymbus Bioscience (BA6), Dako (AT13/5), Immunotech (T16), Pharmingen (HIT2), Sanbio/Monosan (BL-D2, MIG-P12), Sanbio/Monosan/Accurate (BLD2), Seralab and Serotec (B-A6, AT13/5, T16).

Fixation/Preparation
Most antibodies are reactive in fixed paraffin-embedded sections and HIER in Target Retrieval Solution enhances staining (Leong et al, 1997).

Background
The CD 38 molecule, initially described as T10, consists of a single chain of 46 kD, spanning the membrane with its carboxyl terminus located in the extracellular compartment. CD 38 has been one of the most elusive molecules within the family of leukocyte multilineage markers (Reinherz et al, 1980) that has emerged as a multifunctional protein (Mehta et al, 1996). It is expressed on different precursor cells, monocytes, activated T cells and terminally differentiated B cells, including plasma cells (Malavasi et al, 1994). This transmembrane glycoprotein appears to mediate several diverse functions such as signal transduction, cell adhesion (including binding to endothelium), with an important role in lymphocyte homing (Dianzani et al, 1994), and cyclic adenosine diphosphate-ribose synthesis, but its activities remain elusive (Malavasi et al, 1994). Immunoreactivity for CD 38 has also been described in a subset of pyramidal neurons and astrocytes and was predominantly distributed in the perikarya and dendrites in association with rough endoplasmic reticulum, ribosomes, small vesicles, mitochondria and cell membranes (Yamada et al, 1997). CD 38 has also been demonstrated in normal prostate epithelium within both basal and secretory epithelial cells and appeared to be lost in some cases of prostatic carcinoma, hyperplasia and in non-malignant glands surrounding tumor. It was speculated that the role of CD 38 in intracellular calcium mobilization may contribute to smooth muscle contraction and/or sperm motility (Kramer et al, 1995).
The source of the antigen for raising anti-CD 38 specific monoclonal antibody had mainly been preparations obtained from MLC cells, normal thymocytes and the plasmacytoma cell line LP-1 (Alessio et al, 1990). This was used in the context of endometrial biopsy specimens to allow the definitive diagnosis of chronic inflammation to be made (Leong et al, 1997).

Applications
The expression of CD 38 is not restricted to a specific lineage nor to a discrete activation step. It is found on precursor cells in the bone marrow, activated cells (T and B blasts), terminally differentiated cells (such as plasma cells), monocytes and most peripheral blood NK cells (Allessio et al, 1990; Malavasi et al, 1994). CD 4+CD 45RA+ cells also preferentially express CD 38, but the antigen is not expressed by CD 4+CD4 5RO+ cells. From a practical standpoint, CD 38 has been useful in the immunophenotyping of acute leukemias and in research into the role of activated T cells in immunodeficiency diseases and in autoimmune diseases. It is a useful marker for plasma cells as poorly differentiated plasma cells may mimic other blastic lymphoid cells and suboptimal cytomorphologic preservation may impede the accurate recognition of plasma cells (Appendix 1.6). We have found CD 38 to be a better antibody than VS 38 when employed to identify plasma cells such as in the diagnosis of chronic endometritis (Leong et al, 1997), as the latter also stains stromal and endometrial cells, reducing its usefulness in this setting. CD 38 shows strong labeling of plasma cells, enhancing their distinctive cytologic characteristics.

References
•Alessio M, Roggero S, Funaro A et al 1990 CD 38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells. Journal of Immunology 1990; 145: 878-884.

•Dianzani U, Funaro A, DiFranco D et al 1994 Interaction between endothelium and CD4+ CD45RA+ lymphocytes: Role of the human CD 38 molecule. Journal of Immunology 153: 952-959.

•Kramer G, Steiner C, Fodinger D et al 1995. High expression of a CD-38 like molecule in normal prostatic epithelium and its differential loss in benign and malignant disease. Journal of Urology 154: 1636-1641.

•Leong AS-Y, Vinyuvat S, Leong FJWM, Suthipintawong C 1997 Anti-CD 38 and VS 38 antibodies for the detection of plasma cells in the diagnosis of chronic endometritis. Applied Immunohistochemistry 5: 189-193.

•Malavasi F, Funaro A, Roggero S et al 1994 Human CD 38:A glycoprotein in search of a function. Immunology Today 15: 95-97.

•Mehta K, Shahid U, Malavasi F 1996 Human CD 38, a cell-surface protein with multiple functions. FASEB Journal 10: 1408-1417.

•Reinherz EL, Kung PC, Goldstein G et al 1980 Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T cell lineage. Proceedings of the National Academy of Sciences, USA 77: 1588-1592.

•Yamada M, Mizuguchi M, Otsuka N et al 1997 Ultrastructural localization of CD 38 immunoreactivity in rat brain. Brain Research 756: 52-60.

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