GENERATION OF THE GERMLINE PERIPHERAL B-CELL REPERTOIRE - VH81X-LAMBDA-B CELLS ARE UNABLE TO COMPLETE ALL DEVELOPMENTAL PROGRAMS

The generation of VH81X heavy chain lambda-Light chain-expressing B ce lls (VH81X-lambda(+) B cells) was studied in VH81X heavy chain transge nic mice as well as in VH81X JH -/- and VH81X JH -/- Ck -/- mice, in w hich competition resulting from expression of heavy and light chains f rom the endogenous heavy and lambda light chain loci was prevented, We show that although lambda light chain gene rearrangements occur norma lly and give rise to light chains that associate with the transgenic h eavy chain to form surface and soluble IgM molecules, further B cell d evelopment is almost totally blocked, The few VH81X-lambda(+) B cells that are generated progress into a mature compartment (expressing surf ace CD21, CD22, CD23, and low CD24 and having a relatively long life s pan) but they also have reduced levels of surface Ig receptor and expr ess higher amounts of Fas Ag than VH81X-kappa(+) B cells, These VH81X- lambda(+) B cells reach the peripheral lymphoid organs and accumulate in the periarteriolar lymphoid sheath but are unable to generate prima ry B cell follicles, In other heavy chain transgenic mice (MD2, M167, and M54), lambda(+) B cells are generated, However, they seem to be pr eferentially selected in the peripheral repertoire of some transgenic heavy chain mice (M54) but not in others (MD2, M167). These studies sh ow that a crucial selection step is necessary for B cell survival and maintenance in which B cells, similar to T cells, receive signals depe nding on their clonal receptors.