Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies

Abstract

Differentiation of naive B cells into plasma cells or memory cells occurs in the germinal centers (GCs) of lymph follicles or alternatively via a GC- and T-cell-independent pathway. It is currently assumed that B-cell lymphomas correlate to normal B-cell differentiation stages, but the precise correlation of several B-cell lymphomas to these two pathways remains controversial. In the present report, we describe the junctional adhesion molecule C (JAM-C), currently identified at the cell-cell border of endothelial cells, as a new B-cell marker with a tightly regulated expression during B-cell differentiation. Expression of JAM-C in tonsils allows distinction between two CD27+ B-cell subpopulations: JAM-C- GC B cells and JAM-C+ non-germinal B cells. The expression of JAM-C in different B-cell lymphomas reveals a disease-specific pattern and allows a clear distinction between JAM-C- lymphoproliferative syndromes (chronic lymphocytic leukemia, mantle cell lymphoma and follicular lymphoma) and JAM-C+ ones (hairy cell leukemia, marginal zone B-cell lymphoma). Therefore, we propose JAM-C as a new identification tool in B-cell lymphoma diagnosis

Homing of Human B Cells to Lymphoid Organs and B-Cell Lymphoma Engraftment Are Controlled by Cell Adhesion Molecule JAM-C

“…We had previously reported that the expression of JAM-C in B-cell lymphomas revealed a disease-specific pattern, distinguishing JAM-Cpos from JAM-Cneg B-cell lymphomas (13). In Fig.…”

“…Cells were stably transfected using Amaxa Nucleofection System according to manufacturer's instructions with a pcDNA plasmid encoding a neomycin-resistance cassette without (¼pcDNAe) or with full-length human JAM-C cDNA (¼HuJAM-C; ref. 13). After 2 weeks selection with G418, 1 mg/mL (Invitrogen) cells were fluorescence-activated cell sorting (FACS)-sorted and further expanded under G418 selection (600 mg/mL).…”

“…Peripheral blood B cells from normal blood donors ($70% JAM-Cpos cells, 30% JAM-Cneg cells; ref. 13) were injected into mice and human B cells recovered from the organs were stained with anti-huJAM-C antibodies. Percentages of JAM-Cpos and JAM-Cneg B cells were quantified.…”

“…Its differential expression distinguishes memory germinal center B cells (CD27pos, JAMCneg) from memory non-GC B cells (CD27pos, JAM-Cpos; ref. 13). The expression of JAM-C in different B-cell lymphomas allowed the classification into 2 types of B-cell malignancies: JAM-Cneg [chronic lymphocytic leukemia (CLL), follicular lymphoma, and diffuse large B-cell lymphoma (DLBL)] and JAM-Cpos [marginal zone B-cell lymphoma (MZBL) and hairy cell leukemia (HCL)] lymphomas.…”

JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series)

“…Recent reports have shown that JAM-C is expressed on dendritic cells, platelets, and subsets of T and B cells in humans. 23,39,41,43,44,69 To date, however, JAM-C expression has not been reported on mouse leukocytes. 48 The pan-expression of human JAMs across leukocyte and endothelial/epithelial populations has introduced a further level of complexity to interpreting a precise role for these molecules in leukocyte trafficking.…”