Membrane IgD-positive B cells of "low-IgD serum phenotype" individuals fail to secrete IgD and fail to shift to...

IgD production by short-term human peripheral blood mononuclear cell (PBM) cultures was studied to establish the in vitro correlates of low serum IgD expression. Cells of persons with less than 3 micrograms/ml IgD in the serum, referred to as the low-serum IgD phenotype (LISP), were analyzed. Advantage was taken of recently developed data on spontaneous IgD biosynthesis by human B cells and the observation that lambda light chains are preferentially expressed by IgD-secreting cells in vitro. Initial analysis of an IgD serum distribution showed that all LISP sera contained low but detectable amounts of IgD, with a mean value of 0.85 microgram/ml; this figure was 30- to 35-fold lower than the mean of the majority of the population. LISP PBM contained normal numbers of IgD-positive B cells which displayed a normal intensity of IgD per cell using comparative analysis of mean channel fluorescence by cell flow cytometry. Several lines of evidence suggested that IgD-secreting cells could not be generated from LISP lymphocytes in vitro. Namely, it was found that no IgD immunoglobulin-containing cells were found among PBM of LISP persons; cell lysates enriched for the intracellular fraction by Triton X-114 phase separation showed low IgD in LISP cells despite "normal" amounts of IgD in membrane-enriched fraction preparations; there was no spontaneous IgD secretion by any LISP PBM cultures; and neither LISP sera nor cellular IgD preparations showed IgD lambda/kappa ratios greater than 1.0, indicative of the absence of the preferential lambda light-chain expression associated with secretion of IgD.(ABSTRACT TRUNCATED AT 250 WORDS)