Epstein-Barr-virus-transformed lymphoblastoid cell lines derived from patients with X-linked agammaglobulinaemia and Wiskott-Aldrich syndrome: responses to B cell growth and differentiation factors.

Epstein-Barr-virus-transformed B lymphoblastoid cell lines (EBV-transformed LCL) from three patients with X-linked agammaglobulinaemia (XLA), six patients with Wiskott-Aldrich Syndrome (WAS), and seven normal donors, were tested for growth and differentiation in response to human recombinant IL-4, a commercially available, low molecular weight B cell growth factor (BCGFlow), and B cell differentiation factor (BCDF) secreted by the T24 cell line, now known to be IL-6. Proliferation (3H-TdR uptake) by EBV-transformed LCL from both XLA and WAS patients in response to BCGFlow was similar to that obtained with the normal cell lines. In addition, three normal and three WAS, but none of the XLA EBV-transformed LCL, proliferated a little in response to IL-4. All the normal B cell lines secreted IgM, and six out of the seven secreted IgG in response to BCGFlow and BCDF. A similar pattern of response was obtained with the WAS EBV-transformed LCL (6/6 secreted IgM and 4/6 secreted IgG). Several of the normal and WAS EBV-transformed LCL also secreted IgM and IgG in response to IL-4. In contrast, the lines from the XLA patients were abnormal. One secreted large amounts of IgM and two secreted small amounts, but none of the XLA lines secreted IgG constitutively or in response to any of the factors (IL-4, BCDF). The lack of detectable IgG secretion by the XLA lines was probably due to an absence of precommitted IgG B cell precursors transformed by EBV rather than an intrinsic inability to respond to BCGF and BCDF. All of the lines, including those derived from XLA patients, were shown to secrete B cell growth and differentiation factors detected on indicator B cell lines. These results suggest that the abnormal X-linked genes responsible for XLA and WAS do not interfere with B cell responses to B cell growth and differentiation factors.