Reduced Surrogate Light Chain in Old B Cell Precursors Compromises B Lymphopoiesis and Increases B Cell Reactivity to Common Self Antigens

In murine bone marrow, old age (\u3e2 yrs.) is characterized by low production of pre-B and immature B cells, alterations in the “read-out” of the B cell repertoire and increased autoreactivity within mature B cell populations. In addition, there are changes in the composition of B cell subsets: in the bone marrow early CD23 expression on immature B cells is linked to an activated phenotype, while in the periphery there is increased representation of “antigen experienced” B cells, exemplified by Age-associated B cells. I propose that: 1) Old age-associated reductions in expression of the surrogate light chain not only contribute to reduced pre-B and immature B cells in old mice, but also alter the read-out” of the antibody repertoire. 2) Immature B cells in old mice are often phenotypically more activated, anergic, and display altered light chain usage. Changes in immature B cell reactivity to antigen associated with reduced surrogate light chain are also seen in the peripheral B cell populations. 3) Age-associated B cells represent “self-reactive” antigen experienced B cells, provide “feed-back” inhibition of B lymphopoiesis, and promote a “preBCR-deficient” pathway of new B cell production. This in turn alters “read-out” of the mature B cell repertoire