Doctor of Philosophy (PHD)
Microbiology and Immunology (Medicine)
Date of Defense
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Fifth Committee Member
Sixth Committee Member
In murine bone marrow, old age (>2 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.
B cells; B lymphopoeisis; senescence; inflammation; autoreactivity; phosphorylcholine
Khomtchouk, Kelly M., "Reduced Surrogate Light Chain in Old B Cell Precursors Compromises B Lymphopoiesis and Increases B Cell Reactivity to Common Self Antigens" (2016). Open Access Dissertations. 1589.