Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia

Abstract

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out.

Epstein-Barr virus-induced precursor B cell lines from patients with congenital agammaglobulinemia.

“…In conclusion, we have established LCL with the nature of pre-B cells and other precursor B cells from the bone marrow cells of patients with CAG and confirmed the observation of Fu et al (1980). However, we have found more variable patterns of Ig expression, especially with regard to the expression of 6 heavy chains, in the LCL established in our laboratory.…”

“…Recently, Fu et al (1980) have reported that LCL resembling pre-B cells and other possible precursor cells of B cells have been established from EBV infected bone marrow cells of CAG patients suggesting that precursor B cells without Ig synthesis and pre-B cells without surface Ig (slg) could be transformed by EBV, giving rise to LCL which retain the characters of their cell origin, although the target cells for EBV were considered to be B cells with C3d receptors and slg (Yefenof et al 1976; Katsuki et al 1977). In this study we have established LCL with characteristics of precursor B cells from CAG patients, and demonstrated that the LCL established had more diverse patterns of Ig expression than those reported previously.…”

Epstein-Barr Virus Exploits BSAP/Pax5 To Achieve the B-Cell Specificity of Its Growth-Transforming Program

“…During lymphocyte ontogeny, BSAP is first expressed at the multipotent pro-B-cell stage and actually drives the final commitment to the B-cell lineage (27); thereafter, it remains expressed in mature B cells and is only extinguished with the final differentiation to a plasma cell (1). It is therefore interesting that both pro-and pre-B cells have been found to be susceptible to EBV transformation in vitro (13,15,20). By contrast, plasma cells are not transformable, and indeed, the plasmacytic differentiation of LCL cells has been linked to lytic cycle induction and the suppression of Wp/Cp activity (9,34).…”

Ecto-5'-nucleotidase activities in lymphocytes and B lymphoblastoid cell lines from patients with congenital agammaglobulinemia.

“…On the other hand, the LCL from BMM of CAG patients possessed almost the same characteristics as the precursor B cells reported by Fu et al (1980) which lacked slg, clg, and secretion of Ig. They had EBV associated nuclear antigen (EBNA), complement receptors (C3b and C3d), Fe receptors for IgM, Con A receptors, and peanut agglutinin (PNA) receptors.…”