c-Myb is required for plasma cell migration to bone marrow after immunization or infection.
Bottom Line: Here, we detail the critical role of the transcription factor c-Myb in determining plasma cell location.This was correlated with a dramatic reduction of plasma cells in peripheral blood, mislocalization in spleen, and an inability of c-Myb-deficient plasma cells to migrate along a CXCL12 gradient.Therefore, c-Myb plays an essential, novel role in establishing the long-lived plasma cell population in the BM via responsiveness to chemokine migration cues.
Affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia firstname.lastname@example.org email@example.com.Show MeSH
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Mentions: To assess the contribution of c-Myb to a humoral response, we generated c-Mybfl/fl mice carrying a Cd23Cre/+ transgene that deletes c-Myb at the T2 stage of B cell development (Emambokus et al., 2003; Kwon et al., 2008). Strikingly, immunized c-Mybfl/flCd23Cre/+ had no IgG1+ Ag-specific ASCs in the BM (Fig. 1, A–C). Although the frequency of Ag-specific IgG1+ ASCs in the BM of Cd23Cre/+ control mice increased throughout the immune response (Fig. 1 C), there were few or no BM IgG1+ ASCs detected in the absence of c-Myb. This was not due to a lack of production, as assessment of NP+IgG1+ ASCs in the spleen demonstrated comparable frequencies over time (Fig. 1 D). Similarly, affinity maturation of splenic NP+IgG1+ ASCs appeared normal (Fig. 1 E). c-Mybfl/fl mice carrying an AicdaCre/+ allele, in which c-Myb was deleted after Ag activation of mature B cells (Kwon et al., 2008), also revealed a lack of NP+IgG1+ ASCs in the BM during an immune response (Fig. 1 F). This indicates a role for c-Myb during the processes of ASC differentiation and migration rather than in establishing a preexisting condition in naive B cells. NP+ GC B cells formed normally in the absence of c-Myb at day 7 after immunization, but by day 14 there was a twofold decrease, suggesting persistence of these cells was not optimal in the absence of c-Myb (Fig. 1 G). Within the c-Myb–deficient NP+ GC compartment, however, the frequency of IgG1+ cells was increased at day 14 and 28 after immunization compared with controls (Fig. 1 H). Thus, the number of IgG1+NP+ GC B cells, which are arguably the precursors to IgG1+ ASCs in the BM, was similar between knockout and controls at days 7 and 14, and significantly decreased at day 28 (Fig. 1 I). Thus, the lack of ASC in the BM of c-Myb–deficient mice was not caused by an absence of IgG1+NP+ GC B cells.
Affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia firstname.lastname@example.org email@example.com.