Antigen-Selected Immunoglobulin Secreting Cells Found in Spleen

December 31, 2003

Blood First Edition Paper, prepublished online December 30, 2003

Submitted September 11, 2003

Accepted December 19, 2003

Ag*-selected Ig-secreting cells persist in human spleen as well as

bone marrow

I Ellyard, le T Avery, Tri Giang Phan, 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

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**.

*Ag, meaning antigen

**general term for a blood disorder

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