Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.
Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.
Tedoldi
S
S
Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, UK.
Paterson
J C
JC
Cordell
J
J
Tan
S-Y
SY
Jones
M
M
Manek
S
S
Dei Tos
A P
AP
Roberton
H
H
Masir
N
N
Natkunam
Y
Y
Pileri
S A
SA
Facchetti
F
F
Hansmann
M-L
ML
Mason
D Y
DY
Marafioti
T
T
D000311:Adrenal Glands / Q000737:chemistry; D001402:B-Lymphocytes / Q000737:chemistry / Q000648:ultrastructure; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002460:Cell Line; D002540:Cerebral Cortex / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016393:Lymphoma, B-Cell / Q000737:chemistry*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry; D014066:Palatine Tonsil / Q000737:chemistry; D012669:Seminal Vesicles; D013270:Stomach
D015415:Biomarkers; D014408:Biomarkers, Tumor; C486311:IRAG2 protein, human; D008565:Membrane Proteins