In:
The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 1_Supplement ( 2010-04-01), p. 135.5-135.5
Abstract:
AAntibodies secreted by terminally differentiated plasma cells are important in immune defense, but also contribute to the pathogenesis of autoimmune diseases. How do naïve and memory B cells efficiently and promptly undergo terminal differentiation after encountering an antigen remains to be fully understood. We found that in the human tonsil most CD138+ plasma cells are surrounded by CD163+ resident macrophages. This prompted us to explore the role of macrophages in B cell activation. Sorted tonsilar macrophages were co-cultured with autologous IgD+CD27- naïve B or IgD-CD27+ memory B cells that were activated by anti-Ig, CpG and IL-2. Both naïve and memory B cells co-cultured with macrophages underwent significant proliferation and differentiation towards CD138+CD38+ plasma cells, whereas B cells alone failed to do so. A similar finding was obtained by using in vitro-generated macrophages. Such a process was tightly regulated by the dominant production of IP-10 by macrophages and the receptor CXCR3 on B cells. We found that patients with systemic lupus erythematosus (SLE) with active disease display an expansion of CXCR3+ B cells (range 20-90%) compared to those with inactive disease (range 5-15%). Accordingly, serum levels of IP-10 were elevated in active SLE patients. Thus, our data support a previously unrecognized mechanism by which macrophages induce terminal differentiation of plasma cells through secretion of IP-10, which may have potential implications autoimmunity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.184.Supp.135.5
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2010
detail.hit.zdb_id:
1475085-5
