The Low Ionic Strength Reaction of Human Blood: Relationship between the Binding of Serum Immunoglobulin and Complement to Red Blood Cells and Surface Charge of the Cells

S ummary . Using the sucrose haemolysis reaction of Hartmann & Jenkins (1966) as a basic model, the low ionic strength reaction (LISR) of human blood was studied to determine: (1) serum Ig uptake by RBC with saline elution and 125 I‐IgG uptake, and (2) complement fixation (CF) to RBC with lysis of PNH cells and C 3 /C 4 antiglobulin haemagglutination (AH) of normal cells. The saline eluates were found to contain IgG and IgM with traces of IgA; their pH optima for the uptake by RBC were 6.0±0.5, 5.5±0.5 and c 5.0 respectively. The ratio of bound IgG to IgM was linearly related to the uptake pH. Both C 4 AH and lysis were found to be optimum at pH 6.0±7.5, whereas the maximum C 3 AH was at pH 6.0±0.5. The LISR performed at a constant pH (6.1±0.1) showed that an increasing concentration of neuraminidase (VCN) used in pretreatment of RBC was associated with a decrease in both IgG uptake and CF activity. A maximum VCN effect reduced the Ig uptake to c 20% of normal and abolished almost all the CF activity. An impaired LISR to various degrees was also observed with RBC pretreated with ficin, papain, bromelin, trypsin or protamine, and RBC from two individuals of En(a–) type. Preincubation of serum at LIS with and without RBC resulted in respectively a ‘complete’ and partial consumption of C in the fluid phase. The latter was not enhanced or inhibited by the addition of VCN‐treated RBC for preincubation. A hypothesis is proposed suggesting that in the LISR the Ig uptake by RBC is an electrostatic interaction of the oppositely charged RBC and Ig and the CF to RBC results from C activation by the cell‐bound IgG and IgM. In addition, a pH‐dependent inactivation of the cell‐bound C 3 in the LISR is demonstrated.