Low surrogate light chain in pro-B cells from old mice suppresses apoptosis and alters the idiotypes and proportions of phosphorylcholine reactive B cells (LYM6P.718)

Abstract

Abstract The generation of new B cells is substantially decreased in old mice (>2 years). Early B cell precursors (pro-B cells) are reduced in old mice and exhibit a reduction in the surrogate light chain (SLC) protein λ5. We hypothesize that this alters the expression and function of the pre-B cell receptor and influences the “read-out” of antibody specificities in the B cell repertoire. In old mice, the remaining pro-B cells, low in SLC, are resistant to apoptotic stimuli (TNFα), in contrast to young adult pro-B cells. Apoptotic sensitivity reflects levels of the SLC, since young pro-B cells partially or completely deficient in λ5 are also resistant to apoptosis. Age-associated B cells (ABC) represent a B cell subset which expands in old mice; ABC are pro-inflammatory and secrete TNFα. Adoptive transfer of ABC into young RAG-2 KO recipients results in partial loss of pro-B cells and, in particular, loss of pro-B cells with higher levels of SLC λ5. Anti-phosphorylcholine (PC) reactive B cells, especially those of the T15 idiotype, are important in defense against pneumococci. In old age, the proportion of PC reactive B cells, particularly with less protective T15 negative idiotypes, increases. Low SLC promotes both increased PC reactivity and T15 negative idiotypes. These studies suggest that ABC promote an “SLClow” B cell pathway that alters antibody specificities in old age.