Reduction of marginal zone B cells in CD22-deficient mice

Abstract

CD22 is a B cell‐specific member of the immunoglobulin superfamily and binds to sialic acid. CD22 inhibits B cell receptor signaling. Mice deficient for CD22 show a largely normal B cell development. Here, we have performed a detailed analysis of the splenic B cell population and found that the subset of marginal zone (MZ) B cells was selectively reduced in CD22‐deficient mice. CD22‐deficient mice showed a lack of TNP‐ficoll capturing cells in the MZ and a reduced response to TNP‐ficoll, particularly when the antigen was applied intravenously. CD22‐deficient B cells showed both enhanced motility as well as enhanced chemotaxis to certain chemokines. The altered chemokine responsiveness or the higher signaling capacity of CD22‐deficient B cells may lead to the compromised MZ B cell compartment, as both processes have previously been shown to affect MZ composition.

Regulation of Follicular B Cell Differentiation by the Related E26 Transformation-Specific Transcription Factors PU.1, Spi-B, and Spi-C

“…Genes significantly increased in cultured Sfpi1 2/2 Spib 2/2 pro-B cells included CD22 (22-fold), CD9 (7-fold), CD1d (2.7-fold), and HES1 (2-fold). CD22, CD9, and CD1d are expressed at high levels on the surfaces of MZ B cells and are important for MZ B cell development (37,52,53). HES1 is a known target gene of Notch signaling, which is known to be essential for MZ B cell RT-qPCR analysis was performed on RNA prepared from uninfected WEHI-279 cells (black bars) or MIG-3XFLAG-Spi-C-infected WEHI-279 cells (gray bars) for genes indicated on the x-axis.…”

Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice

“…Several studies have suggested a potential role for marginal zone B cells in the spontaneous production of autoantibodies in SLE, usually associated with an increase of the population of these B cells [20][21][22]. However, some studies of genetically manipulated mice with lupus-like autoimmunity have also shown an impaired development of the marginal zone B cells and suggested that this could be due to defects in chemotactic migration to the marginal zone and/or to hypersensitive B cell receptor signaling, favoring an accelerated maturation toward follicular B cells [23][24][25][26][27]. The C1qa -/-mice displayed hyperreactive B cells as judged by the increase of activation markers, and thus one can speculate that the observed reduction of marginal zone B cells is related to an increased activation of autoreactive B cells, and their exit toward the follicular zone associated with the development of autoimmune responses occurring in these mice.…”

Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

“…A possible explanation for the decreased antibody response is that there are fewer MZ B cells in the FcμR-deficient mice. However, a decrease in MZ B cells does not necessarily lead to impaired antibody responses (35,36). Moreover, MZ B cells are more notable for their participation in TI responses than in TD responses.…”