The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein.

Abstract

The human B lymphocyte-associated CD37 antigen (gp40-52) has been characterized by the monoclonal antibody HD28. The CD37 antigen is strongly expressed on surface immunoglobulin positive B lymphocytes and weakly on a subpopulation of T lymphocytes and myeloid cells. The total molecular mass of the antigen ranges from approximately 40 to 52 kDa in B cell-derived leukemias and malignant lymphomas as well as in normal and anti-mu/B cell growth factor-activated tonsillar B cells. The polydisperse nature of the electrophoretic pattern of the CD37 antigen was found to be due to a microheterogeneity in its carbohydrate moiety. Biochemical analysis showed that the CD37 antigen derived from B cell-lines BJAB and LICR-LON-HMy2 consists of a single chain protein core of approximately 25 kDa to which two N-linked, complex carbohydrate antennae of various length are bound. The glycosylation of the molecule comprises about 50% of the total molecular mass. The molecule does not contain O-linked carbohydrate chains. In contrast, the non-Hodgkin's lymphoma cell line, OCI.LY1, which is growth-dependent on human serum, carries a CD37 antigen with an additional carbohydrate chain resulting in a total molecular mass of approximately 40 to 64 kDa. At the electron microscopy level, this cell surface-expressed antigen was found to be associated with intracellular vesicles. The subcellular distribution of the CD37 antigen may reflect a function of this antigen both at the cell surface and in the cytoplasm. We found that, both due to its peculiar biochemical structure and its ultrastructural distribution, the CD37 antigen closely resembles the 46-kDa species of the mannose 6-phosphate receptor. The implications of this possible congruence for the function of the CD37 antigen are discussed.

Potent Preclinical Efficacy of DuoHexaBody-CD37 in B-Cell Malignancies

“…Nonetheless, many patients develop resistance against CD20‐targeting therapies, with little or no further treatment options 1 . Tetraspanin CD37 is expressed almost exclusively on hematopoietic cells with high expression on mature B‐cells, including their malignant counterparts, 2,3 and is a well described and validated target for B‐cell malignancies. A number of CD37 targeting agents are in (pre)clinical development, including antibody‐drug conjugates (IMGN529 and AGS67E), an Fc‐engineered antibody (BI836826), a homodimeric therapeutic protein (otlertuzumab/TRU‐016), a radioimmunoconjugate ( 177 Lu‐lilotomab), and chimeric antigen receptor T‐cells 4‐6 .…”

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish

“…To identify cell types and states at chosen clustering resolution (0.6 for control only, 0.5 for control and infected integrated), we performed differential expression analysis using Wilcoxon rank sum-based method (log2 fold change > 0.25, % of expressing cells > 0.25). Known markers were used to identify T cells ( cd247l , lck , il7r , and cxcr4a ) ( 58 – 60 ), dendritic cell-like populations ( ctsbb , tlr7 ) ( 61 , 62 ), B cells ( cd37 , pax5 ) ( 63 , 64 ), macrophages ( mpeg1.1 , grn1 ) ( 65 , 66 ), neutrophils ( mpx , il6r ) ( 11 , 67 ), erythrocytes ( hbba2 , hemgn ) ( 68 ), thrombocytes ( thbs1b , fn1b ) ( 62 ), superficial epithelial cells ( krt1-19d , cldne ) ( 69 ), ionocytes ( trpv6 , foxi3b ) ( 70 ), intermediate epithelial cells ( cldna , tp63 ) ( 69 ), basal epithelial cells ( cldn1 , cldni ) ( 69 ), mesenchymal cells ( vcana , clu ) ( 71 ), lateral line-like cells ( prox1a , prr15la ) ( 72 ), and epidermal mucous cells ( agr2 , cldnh ) ( 69 ). We found one population with some cells locating closer to the T cell populations but without clear enrichment for known signatures and included this population for a subclustering analysis with other T cells.…”

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish

“…To identify cell types and states at chosen clustering resolution (0.6 for Control only, 0.5 for Control and Infected integrated), we performed differential expression analysis using Wilcoxon rank sum-based method (log2 fold change > 0.25, % of expressing cells > 0.25). Known markers were used to identify T cells (cd247l, lck, il7r, and cxcr4a) (53)(54)(55), dendritic cell-like populations (ctsbb, tlr7) (56,57), B cells (cd37, pax5) (58,59), macrophages (mpeg1.1, grn1) (60,61), neutrophils (mpx, il6r) (11,62), erythrocytes (hbba2, hemgn) (63), thrombocytes (thbs1b, fn1b) (57), superficial epithelial cells (krt1-19d, cldne) (64), ionocytes (trpv6, foxi3b) (65), intermediate epithelial cells (cldna, tp63) (64), basal epithelial cells (cldn1, cldni) (64), mesenchymal cells (vcana, clu) (66), lateral line-like cells (prox1a, prr15la) (67), and epidermal mucous cells (agr2, cldnh) (64). We found one population with some cells locating closer to the T cell populations but without clear enrichment for known signatures and included this population for a subclustering analysis with other T cells.…”