The Journal of Experimental Medicine
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Published online 18 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1745/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1745-1754

Original Article

Antigen-Independent Appearance of Recombination Activating Gene (Rag)-Positive Bone Marrow B Cells in the Spleens of Immunized Mice

Frank Gärtnera, Frederick W. Alta, Robert J. Monroea, and Katherine J. Seidla

a The Howard Hughes Medical Institute, the Children's Hospital, the Center for Blood Research, and the Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115
The Howard Hughes Medical Institute, the Children's Hospital, Enders 861, 300 Longwood Ave., Boston, MA 02115.617-738-0163617-355-7290

alt{at}rascal.med.harvard.edu

Splenic B lineage cells expressing recombination activation genes (RAG+) in mice immunized with 4-hydroxy-3-nitrophenyl-acetyl coupled to chicken {gamma}-globulin (NP-CGG) and the adjuvant aluminum-hydroxide (alum) have been proposed to be mature B cells that reexpress RAG after an antigen encounter in the germinal center (GC), a notion supported by findings of RAG expression in peripheral B lymphocyte populations activated in vitro. However, recent studies indicate that these cells might be immature B cells that have not yet extinguished RAG expression. Here, we employ RAG2–green fluorescent protein (GFP) fusion gene knock-in mice to show that RAG+ B lineage cells do appear in the spleen after the administration of alum alone, and that their appearance is independent of T cell interactions via the CD40 pathway. Moreover, splenic RAG+ B lineage cells were detectable in immunized RAG2-deficient mice adoptively transferred with bone marrow (BM) cells, but not with spleen cells from RAG+ mice. Although splenic RAG+ B cells express surface markers associated with GC B cells, we also find the same basic markers on progenitor/precursor BM B cells. Finally, we did not detect RAG gene expression after the in vitro stimulation of splenic RAG– mature B cells with mitogens (lipopolysaccharide and anti-CD40) and cytokines (interleukin [IL]-4 and IL-7). Together, our studies indicate that RAG+ B lineage cells from BM accumulate in the spleen after immunization, and that this accumulation is not the result of an antigen-specific response.

Key Words: alum • germinal center • receptor editing • immunoglobulin re-rearrangement

Abbreviations used in this paper: alum, aluminum-hydroxide; B6, C57BL/6; bi, biotin; BM, bone marrow; CyC, CyChrome; GC, germinal center; GAPDH, glyceraldehyde 3-phosphate dehydrogeanse; GFP, green fluorescent protein; HSA, heat stable antigen; NP-CGG, 4-hydroxy-3-nitrophenyl-acetyl coupled to chicken {gamma}-globulin; PNA, peanut agglutinin; RAG, recombination activating gene; RT, reverse transcription; wt, wild-type.

© 2000 The Rockefeller University Press


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