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However, natalizumab has been associated with the development of progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus (JCV) infection. In order to improve our understanding of the mechanism of action of natalizumab and to identify possible risk factors for PML development, we have characterized in detail the cell blood composition in MS patients treated with natalizumab for more than 30 months. Natalizumab induced the release of lymphoid\u2010 but not myeloid precursor cells, which resulted in a chronic increase ofT\u2010, NK\u2010 and particularly B cells. While the percentage of recent thymic emigrants (RTEs), na\u03cave, effector or memory T cells remained unchanged during treatment, a higher percentage of memory\u2010 and marginal zone (MZ)\u2010like, but not of na\u03cave B cells, was observed, which most likely is due to a decreased retention of these cells within the splenic MZ. The ability of natalizumab to influence B\u2010cell migration and homeostasis through the splenic MZ, where JCV has been detected, adds to the list of natalizumab effects and may contribute to PML development by disseminating JCV.<\/jats:p>","DOI":"10.1002\/eji.201142108","type":"journal-article","created":{"date-parts":[[2011,12,5]],"date-time":"2011-12-05T13:23:02Z","timestamp":1323091382000},"page":"790-798","source":"Crossref","is-referenced-by-count":101,"title":["Natalizumab treatment perturbs memory\u2010 and marginal zone\u2010like B\u2010cell homing in secondary lymphoid organs in multiple sclerosis"],"prefix":"10.1002","volume":"42","author":[{"given":"Raquel","family":"Planas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilijas","family":"Jelc\u0306i\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Schippling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Sospedra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,27]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.12.noc80051"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20858"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/356063a0"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808909106"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20859"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-112052"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-120329"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.381"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000327671.91357.96"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2010.328"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.02.010"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000302687"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051782"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051847"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70006-5"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70040-5"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/597126"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.080708.082655"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198802043180507"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490270405"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.10.7004-7012.1996"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90909-9"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510385834"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/597117"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/344280"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2006.04.011"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.4.428"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.10.1383"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.128.2.844"},{"key":"e_1_2_1_31_2","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.4049\/jimmunol.160.10.5113","article-title":"Intrinsic differences in L\u2010selectin expression levels affect T and B lymphocyte subset\u2010specific recirculation pathways","volume":"160","author":"Tang M. 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