2 MATURATION-ASSOCIATED MOUSE ERYTHROCYTE RECEPTORS OF HUMAN B-CELLS .1. IDENTIFICATION OF 4 HUMAN B-CELL SUBSETS

Abstract

Using rosetting tests with untreated mouse erythrocytes (M) and pronase-treated M (pro M), 4 human B cell subsets can be identified. Three of these, possessing the phenotypes BM+proM+, BM-proM+ or BM-pro-, constitute 17, 61 and 22% of normal blood B cells, respectively. The 4th subset, BM+proM-, does not occur in normal tissues but was found in the pre-B cell line of human lymphoblastoid Raji cells, indicating that this phenotype may be a marker for early B cells. Some differences in the proportion of each subset were found in cord blood, lymph nodes and tonsils. Surface-Ig-positive (SIg+) and -negative (SIg-) non-T cells were present in each subset. M and pro-M rosetting tests were applied to cells from blood of 27 cases of chronic lymphocytic leukemia (CLL) and to cells from involved nodes, spleen or marrow in 5 cases of non-Hodgkin''s lymphoma (NHL). In 15 cases of CLL, there was considerable increase in the BM+proM+ subset (BM+proM+ type CLL); in 7 cases there was a predominance of BM-proM+ cells and in another 4 cases, BM-proM- cells predominated. All 5 cases of NHL were greatly enriched in BM-proM- cells. There was no obvious correlation between rosetting and other surface markers but BM-proM- clones in CLL or NHL always stained brightly with fluorescein isothiocyanate anti-Ig. This was not found in BM+proM+ or BM-proM+ clones. Rosette formation of neuraminidase-treated B cells with M identifies the same subset as B-pro-M rosetting in normals and CLL. Two types of receptors appear to be involved in M and pro-M rosetting, designated R1 and R2, binding to corresponding M ligands L1 and L2, M rosetting is due to R1-L1 binding while R2-L2 binding mediates B-pro-M rosetting. Shifts between subsets within the same clone in some cases of CLL suggest that the subsets are distinct maturational stages of B-cell development rather than families of B cells of different lineage. The following B-cell maturation sequence is proposed: R1+ R2- .fwdarw. R1+ R2+ .fwdarw. R1- R2+ .fwdarw. R1- R2-.