Analysis of B-cell abnormalities in autoimmune mice by in vitro culture system using two types of bone marrow stromal cell clone.

B-cell abnormalities in 4-week-old autoimmune NZB and NZB/WF1 mice were studied with an in vitro culture system using two types of stromal cell clone, ST2 and PA6. ST2 supports B lymphopoiesis, and PA6 maintains B progenitors which do not express a B-lineage antigen (B220), but does not allow their further differentiation into B220+ B-lineage cells. B progenitors developed into B-lineage cells when transferred to the ST2 layer. B-lineage cells generated in this way showed hyperproliferation autoimmune mice, and the frequencies of B-lineage cells in the bone marrow of these mice were high. In contrast, the frequencies of B progenitors in the bone marrow were low. These results suggest that abnormal B-cell formation in autoimmune bone marrow appears at a very early stage of B-cell differentiation, and that B-lineage cells are hyperactive on the ST2 layer in the absence of microenvironmental elements from autoimmune bone marrow. This study indicates that autoimmune B-cell abnormalities can be reproduced in vitro, giving new data at the level of committed B progenitors, suggesting that this culture system will be a useful tool for investigating haemopoietic stem-cell abnormalities in autoimmune mice.