In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules

Abstract

The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114-partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response.