Transitional B cell: Difference between revisions

'''Transitional B cells''' are [[B cells]] at an intermediate stage in their development between bone-marrow (BM) immature cells and mature B cells in circulation. Primary B cell development takes place in the [[bone marrow]], where immature [[B cell]]s must generate a functional [[B-cell receptor|B cell receptor]] (BCR) and overcome negative selection induced by reactivity with [[autoantigens]].<ref name="sims">{{cite journal |title=Identification and characterization of circulating human transitional B cells |authors=Sims GP, Ettinger R, Shirota Y, Yarboro CH, Illei GG, Lipsky PE |journal=Blood|date=1 June 2005 |volume= 105|issue=11|pages=4390-8 |pmid= 15701725 |pmc=1895038 |doi= 10.1182/blood-2004-11-4284}}</ref>

Cells that are developmentally intermediate between immature bone marrow (BM) B lineage cells and fully mature naive B cells in the peripheral blood (PB) and secondary lymphoid tissues are termed ‘transitional B cells’. This term was first used in the mouse in 1995. It is postulated that the transitional cells, after leaving the BM, are subjected to peripheral checks to prevent the production of autoantibodies.<ref>{{cite journal |authors=Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC.|title= Predominant autoantibody production by early human B cell precursors|journal= Science|date= 2003|volume=301|pages=1374–1377 |pmid=12920303 |doi= 10.1126/science.1086907}}</ref> Transitional B cells that survive selection against autoreactivity develop eventually into naive B cells.<ref>{{cite journal|authors=Suryani S, Fulcher DA, Santner-Nanan B, et al. |title=Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells|journal= Blood|date= 2010|volume=115|pages=519–529|pmid= 19965666 |doi= 10.1182/blood-2009-07-234799}}</ref> Given the fact that only a small fraction of immature B cells survive the transition to the mature naive stage, the transitional B cell compartment is widely believed to represent a key negative selection checkpoint for autoreactive B cells.<ref>{{cite journal|title=Transitional B cells are the target of negative selection in the B cell compartment|authors= Carsetti R, Köhler G, Lamers MC |journal=J Exp Med. |date=1 June 1995 |volume= 181|issue=6|pages=2129-40 |pmid= 7760002 |pmc=2192072}}</ref><ref>{{cite journal|title=B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals|authors= Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, Lamers MC, Carsetti R |journal=J Exp Med.|date=5 July 1999 |volume= 190|issue=1|pages=75-89|pmid=10429672 |pmc=2195560}}</ref> All transitional B cells are heat-stable antigen (HSA) relative to their mature counterparts and express the phenotypic surface markers AA4.<ref>{{cite journal |authors=Allman D, Li J, Hardy RR |date= 1999|title= Commitment to the B lymphoid lineage occurs before DH–JH recombination|journal= J. Exp. Med. |volume=189|pages= 735–740 |pmid=9989989 |pmc=2192940 }}</ref>

As in the mouse, human transitional cells can be found in the bone marrow, peripheral blood, and spleen. However, in contrast to the nuanced models proposed in the mouse, thus far human studies have, by and large, described a rather homogenous population of transitional B cells (T1/T2) defined by the expression of high levels of CD24, C38 and CD10.<ref name="sims"/><ref name="cuss">{{cite journal|title=Expansionoffunctionally immature transitional B cells is associated with human-immunodeficient states characterized by impaired humoral immunity |authors=Cuss AK, Avery DT, Cannons JL, Yu LJ, Nichols KE, Shaw PJ, Tangye SG |journal=J Immunol.|date=1February 2006 |volume= 176|issue=3|pages=1506-16 |pmid= 16424179 |url=http://www.jimmunol.org/content/176/3/1506.long }}</ref> Overall there is general agreement on the

markers used to separate the subpopulations, although some differences exist in the number of subgroups and in the functional characteristics of the T2 population. T1 B cells are distinguished from the other subsets by the following surface marker characteristics: they are IgMhiIgD-CD21-CD23-, whereas T2 B cells retain high levels of surface IgM but are also IgD+CD21+ and CD23+.<ref name="cuss"/> Differences in functional characteristics of the T2 subpopulation reported by different laboratories are unexplained, although they might be due to differences in isolation strategies. In any case, there is consensus that T2 B cells clearly differ functionally from T1 B cells.<ref>{{cite journal |authors=ChungJB, Sater RA, Fields ML, EriksonJ, Monroe JG|date= 2002 |title=CD23 defines two distinct subsets of immature B cells which differ in their responses to T cell help signals|journal= Int. Immunol. |volume=14|pages= 157–166|pmid=11809735 }}</ref>