Precursor B cells transformed by Epstein-Barr virus undergo sterile plasma-cell differentiation: J-chain expression without immunoglobulin.
Human bone marrow cells were depleted of B lymphocytes to enrich for precursor B cells that could be transformed with Epstein-Barr virus. Transformed immunoglobulin-negative precursors either maintained their immunoglobulin genes in the germ-line configuration or had undergone DJ or abortive VDJ rearrangements (V, D, and J represent variable, diversity, and joining gene segments). All cell lines and their derivative clones, even those with no detectable immunoglobulin gene rearrangements, generated subpopulations of cells that produced high levels of joining (J) chain when analyzed by immunoprecipitation after biosynthetic labeling and by blot hybridization of cytoplasmic RNA. Morphologic and immunofluorescence analyses revealed that J-chain production was confined to clonal progeny that had exited the cell cycle to undergo plasma-cell differentiation. Analysis of cell surface antigens revealed expression of several B-cell maturational markers, including complement receptor type 2 (CR2) and plasma cell antigen 1 (PCA-1). Epstein-Barr virus can thus transform B-cell progenitors, allowing them to proliferate and undergo terminal B-cell differentiation coupled with J-chain expression. These events appear to occur independently of the immunoglobulin gene status of the transformed cells.
Kubagawa
H
H
Department of Pathology, University of Alabama, Birmingham 35294.
Burrows
P D
PD
Grossi
C E
CE
Mestecky
J
J
Cooper
M D
MD
D000361:Agammaglobulinemia / Q000473:pathology; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000196:embryology / Q000473:pathology; D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D002648:Child; D002675:Child, Preschool; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000096:biosynthesis* / Q000235:genetics; D007223:Infant; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology*
D007144:Immunoglobulin J-Chains