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Controversy exists regarding isotype-related differences in the antibacterial and protective properties of lipopolysaccharide (LPS)-specific antibodies of the immunoglobulin M (IgM) class and various IgG subclasses. To clarify this issue, a murine hybridoma secreting IgM monoclonal antibody (MAb) specific for the O polysaccharide of Pseudomonas aeruginosa serogroup O6 LPS was class switched, by sib selection, to produce an IgG3 MAb with identical specificity and variable region heavy and light chain nucleotide sequences. This IgG3-secreting cell line was further switched to the production of O-specific, variable region-identical IgG1, IgG2b, and IgG2a MAbs. Functional comparisons of these LPS-specific IgM and IgG MAb isotypes revealed similar LPS binding, opsonic, and protective activities. Relatively minor isotype-related differences in levels of efficiency of MAbmediated, complement-dependent opsonophagocytic killing (IgM > IgG2a > IgG3 > IgG2b > IgG1) were not associated with corresponding differences in in vivo functions. These findings, in conjunction with previously published data, support a cautious approach to generic conclusions regarding the immunotherapeutic superiority of LPS-specific antibodies belonging to either the IgM or IgG class or to a particular IgG subclass.

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SUMMARYA soluble form of complement receptor 2 (sCR2) is found in normal human serum. Amounts present are about 30-90 ng/ml, which is of the same order as reported for soluble CR1. Although B cells express surface CR2 and are the main peripheral blood source of sCR2 they do not appear to be the major tissue source of serum sCR2. Serum levels of sCR2 of patients with hypogammaglobulinaemia were not significantly different from those of normal individuals even in the case of two brothers with Bruton's X-linked agammaglobulinaemia (XLA) lacking (CD19+) B cells. On gel filtration through Sephacryl S-300 the sCR2 from XLA serum behaved exactly like sCR2 from normal serum or sCR2 affinity purified from cell supernates of a B lymphoblastoid line or from the T-ALL line MOLT-4. In all cases a single peak appeared at the same point in the chromatogram. Possible alternative sources of serum sCR2 are follicular dendritic cells (FDC) which are known to express CR2 strongly and T6+ lymphocytes within the thymus. Peripheral T cells from adults have not been reported to express CR2. However, investigation showed that cells from the Bruton's XLA cases produced small amounts of sCR2 in culture and although no CD21 was detected on the surface of the mononuclear cells by flow cytometry, the more sensitive direct antibody rosette test readily detected CD2 1. Further studies showed that non-B cells from control samples of cord blood or blood of young children also weakly expressed CD21.