Marked depletion at the late pro-B cell stage in the bone marrow of lpr mice correlates with the development of lymphadenopathy but not autoimmunity.
We have found that old lpr mice exhibit a loss of mature B cells in the bone marrow. The deleted population is HSAlo B220hi and is generated from the peripheral pool. Abnormalities in the microenvironment could explain the absence of mature B cells. Thus, old lpr bones were grafted under the skin of normal adult Ly5.1 hosts and examined 3 weeks later for the presence of Ly5.1+ B220hi cells. Our data show that the lpr medullary compartment was efficiently restored by host B cells. These results suggest that the bone marrow microenvironment of old lpr mice is able to sustain mature B cells. However, transfer of T cell-depleted bone marrow cells from old lpr mice to Rag-2 -/- mice leads to incomplete and inefficient repopulation of the host medullary compartment. Thus, a defect at an early stage of B cell differentiation was detected: using four-color flow cytometry, we found a profound depletion of the late pro-B B220+ CD43+ HSA+ BP-1+ cell population in aging lpr mice. This depletion was not observed in old autoimmune-prone MRL-+/+ mice which develop only autoantibodies but was present in B6-lpr mice which develop a lymphadenopathy and an indolent autoimmune syndrome. Altogether, our results demonstrate an age-linked defect in the progression of B cell differentiation in lpr mice independent of the presence of autoantibodies and targeted to the late pro-B cell subset.
Dautigny
N
N
U.345 INSERM, Institut Necker, Paris, France.
Chabre
H
H
Garcia
C
C
Ezine
S
S
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008206:Lymphatic Diseases / Q000209:etiology*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D051379:Mice
D001323:Autoantibodies; D017493:Leukocyte Common Antigens