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

The “IgD paradox” describes the unexpected finding that, despite a predominance of kappa (x) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (λ) type. This potentially informative phenomenon appears to be based on a preferential association between delta (δ) heavy (H) and λ 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,λ/x ratios due to parallel shifts in total IgD and IgD,λ while IgD,x remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of λ 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 λ 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 δ-λ chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD,λ/x ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential δ-λ chain association was studied using Triton X-114-partitioned cell lysates. IgD,λ/x ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD,x predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2–4 times higher supernatant IgD,λ/x ratios. The restriction of high IgD,λ/x 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,λ/x ratio values was consistent with secreted sera IgD showing preferential λ chain expression. It was concluded that the phenomenon of δ-λ chain preferential association is (a) expressed in vitro as well as in vivo; (b) a property of normal, nonmalignant human IgD-secreting B cells; and (c) closely related to the secretory form of IgD. In certain cultures, the δ-λ chain preference was so striking as to imply limited heterogeneity of the IgD immune response.