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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2795-2798.
Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-05-1632.

Submitted May 21, 2003
Accepted October 5, 2003
Mantle cell lymphoma with t(11;14) and unmutated or mutated VH genes expresses AID and undergoes isotype switch events
Gavin Babbage, Richard Garand, Nelly Robillard, Niklas Zojer, Freda K Stevenson, and Surinder S Sahota*
Tenovus Laboratory, Southampton University Hospitals, Southampton, United Kingdom
Laboratoire d'Hematologie, Institut de Biologie des Hopitaux, Nantes, France
* Corresponding author; email: s.s.sahota{at}soton.ac.uk.
Isotype switch commonly follows onset of somatic hypermutation in the germinal center (GC), with activation induced cytidine deaminase (AID) a pre-requisite. Mantle cell lymphoma (MCL) with t(11;14) includes a subset with unmutated (UM) and a minor subset with mutated (MUT) VH genes. Here, we investigated whether switch events and AID expression occur in MCL. In 4/6 UM and 4/7 MUT MCL, alternative tumor-derived C , , transcripts were identified. AID transcripts, including a splice variant were common to both subsets. AID expression correlated with switch in 8/8 cases, but in 3/5 cases occurred with switch absent. Circle transcripts (I -Cµ/I -Cµ) were identified in 5/7 evaluated cases. In 1/12 cases, 12% of tumor cells expressed IgL-restricted sIgA. On-going switch recombination events appear to be a feature of MCL, likely restricted to a minor tumor subpopulation, with occasional variant sIg expression. UM MCL implicate origins from pre-GC B-cells, and reveal switch events at ectopic sites.

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