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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3805-3812.
Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-09-3109.

Submitted September 11, 2003
Accepted December 19, 2003
Ag-selected Ig-secreting cells persist in human spleen as well as bone marrow
Julia I Ellyard, Danielle T Avery, Tri Giang Phan, Nathan J Hare, Philip D Hodgkin, and Stuart G Tangye*
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia; University of Sydney, Sydney, NSW, Australia
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia
Walter and Eliza Hall Institute, Parkville, VIC, Australia
* Corresponding author; email: s.tangye{at}centenary.usyd.edu.au.
Plasma cells (PC) represent the final stage of B cell differentiation and are devoted to the production of Ig. Perturbations to their development can result in human disorders characterised by PC expansions and hypergammaglobulinaemia. Ig-secreting cells (ISC) have been identified in secondary lymphoid tissues and bone marrow (BM). The majority of ISC in lymphoid tissues are short-lived; in contrast, ISC that migrate to the BM become long-lived PC and continue to secrete Ig for extended periods. However, a small population of long-lived PC has been identified in rodent spleen suggesting PC may persist in secondary lymphoid tissues and that the spleen, as well as the BM, plays an important role in maintaining long-term humoral immunity. For these reasons, we examined ISC in human spleen and identified a population that appears analogous to long-lived rodent splenic PC. Human splenic ISC shared morphological, cellular, molecular and functional characteristics with long-lived PC in BM, demonstrating their commitment to the PC lineage. Furthermore, detection of highly mutated Ig V region genes in splenic ISC suggested they are likely to be Ag-selected and secrete high affinity Ig. Thus, our results suggest that splenic ISC have an important role in humoral immunity and may represent the affected cell type in some B-cell dyscrasias.

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