In vitro generation of B lymphocytes in mouse foetal liver, a mammalian 'bursa equivalent'

THERE is good evidence that in birds a haemopoietic stem cells of yolk sac origin 1,2 differentiate into immunoglobulin-bearing lymphocytes in the bursa of Fabricius 3 . The differentiated lymphocytes then migrate to the peripheral lymphoid tissues 4,5 , where they constitute the bursa-derived B lymphocyte population. The primary site(s) of B lymphocyte development in mammals, however, has remained a mystery, with gastrointestinal associated lymphoid tissues 6 (including appendix 7 , tonsils 8 and Peyer's patches 9 ) and haemopoietic tissues 10–12 generally considered the main candidates for mammalian ‘bursa equivalent’. Here we report the development of IgM, IgG and probably IgA-bearing lymphocytes in organ cultures of mouse foetal liver removed at 14 d gestation, a time well before immunoglobulin-bearing cells or cells of lymphoid morphology could be detected in the intact animal. These studies indicate that foetal liver is a bursa equivalent in mice and that gastrointestinal lymphoid tissues are not a sine qua non for the initial development of B cells. In addition, they provide evidence that IgG and probablv IgA-bearing B lymphocytes can develop in the absence of T lymphocytes.