Lymphoid cell lines from patients with "non-secretory" agammaglobulinemia produce glycosylated heavy chains which are reduced in molecular weight.

B lymphocytes from patients with "non-secretory" agammaglobulinemia synthesize but do not secrete Ig. A previous study attributed this secretion failure to a failure of the cells to glycosylate Ig. We examined four B cell lines from three patients with "non-secretory" agammaglobulinemia as a model of this disease. All four cell lines synthesized IgG or IgM in quantities comparable to that produced by normal cell lines, but failed to secrete Ig of either isotype. Molecular weight determination in SDS-polyacrylamide slab gels showed that the heavy chains produced by these cell lines were reduced in size compared to normal: gamma of 49,000 daltons and mu of 59,000 daltons (compared to 55,000 and 68,000 daltons for normal, respectively). Radioactive precursors of the Ig carbohydrate moiety were specifically incorporated into these Ig molecules, suggesting that the reduction in size was not due to failure to glycosylate the Ig. Tunicamycin treatment of the B cell lines resulted in an apparent reduction in size of these already small heavy chains, confirming that the observed reduction in size was not due to the absence of carbohydrate from the Ig molecules. Electrophoresis of cellular IgG and IgM under nonreducing conditions indicated that the molecules were incompletely assembled, lacking disulfide bridging between H (both gamma and mu) chains and L chains. The discrepancy in incorporation of carbohydrate between our studies with "non-secretory" B cell lines and a previous study of "non-secretory" lymphocytes in short term culture led us to reexamine Ig glycosylation in short term cultures. We found that mitogenically stimulated lymphocytes from three patients incorporated radioactive carbohydrate precursors into Ig. These results indicate that the failure of "non-secretory" B cells to secrete Ig is not secondary to a failure of glycosylation, either in short term cultures of B lymphocytes or in B cell lines. Rather, our studies of "non-secretory" B cell lines suggest that there is a polypeptide deletion of the gamma and mu heavy chains, indicated by reduced molecular weight, incomplete assembly of H and L chains, with consequent failure to be secreted, resulting in "non-secretory" agammaglobulinemia.