Etiology of congenital agammaglobulinemia: Growth defect of precursor B lymphoblastoid cell lines and immunoglobulin gene rearrangements.

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Epstein-Barr virus (EBV) induced B lymphoblastoid cell lines (B-LCL) were established from bone marrow cells of the patients with congenital agammaglobulinemia (CAG).We found several immature B-LCL, some of which possess no cell-surface and cytoplastic immunoglobulins, or possess only cytoplasmic heavy chains. We examined the mode of expression of B-cell associated antigens on EBV-induced B-LCL and failed to detect any CAG specific and developmental stage-specific expression of known B-cell related antigens on those B-LCL. These facts indicate that expression of B cell associated antigens on EBV-induced B-LCL does not depend on the developmental stage of B cells, rather depend on the state of EBV infections.If we can detect LCL which express immunoglobulins with very unusual manner, those LCL will probably give us oppotunities to elucidate the etiology of CAG. Fortunately we found 2 such cell lines, K5 and K4, from the same CAG patient. K5 was very unique because they expressed only IgD (delea,lambda) on the surface and produced IgD. K4 was also very unique because they produced lambda heavy chain, and both kappa and lambda light chains. Cell cloning experiments repeated 3 times definitely confirmed that K4 cells produced both kappa and lambda light chains with single mu chains. The pattern of immunoglobolin production seen on K4 and K5 was probably the first ones in the literature. We are going to clone immunoglobuline genes of K4 and K5, and to elucidate the genetic mechanism of the expression of unusual immunoglobulins.