Surface and functional characteristics of B cells from lupus-prone murine strains

Theofilopoulos, Argyrios N.; Balderas, Robert; Gozes, Y.; Fidler, John M.; Liu, Fu‐Tong; Ahmed, Aftab; Dixon, Frank J.

doi:10.1016/0090-1229(82)90110-6

Cited by 13 publications

(6 citation statements)

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“…It could be caused by better activation by the mitogens or a better response to T cellderived factors. The first possibility is less likely since our studies (12) and those of Raveche et al (13) indicate that B cells of 1-mo-old BXSB and NZB/W mice do not show different patterns of LPS-or anti-#-induced activation, i.e., cells in the S+G2+M phase of the cell cycle, than normal B cells. Furthermore, Lyb-5 + B cells, which are thought to respond to anti-/~ are present in normal or near normal numbers in SLE mice (12).…”

Section: Discussionmentioning

confidence: 57%

“…The first possibility is less likely since our studies (12) and those of Raveche et al (13) indicate that B cells of 1-mo-old BXSB and NZB/W mice do not show different patterns of LPS-or anti-#-induced activation, i.e., cells in the S+G2+M phase of the cell cycle, than normal B cells. Furthermore, Lyb-5 + B cells, which are thought to respond to anti-/~ are present in normal or near normal numbers in SLE mice (12). Thus, it appears that the increased response of BXSB and NZB/W B cells is not due to recruitment of more B cells by mitogens, but rather to a true hyperre-sponse of their activated B cells to accessory T cell-derived signals.…”

Section: Discussionmentioning

confidence: 57%

“…In a previous study, we reported on the proliferative responses of splenocytes from various murine strains to LPS and anti-# in high cell density cultures (5 × 105/250 #1) (12). At that density there was no consistent difference in proliferative responses of young autoimmune and young normal mice.…”

Section: Lps-and Anti-#-mediated Proliferation In Low and Medium Densmentioning

confidence: 99%

“…Both B and T cell abnormalities have been reported, and the relative importance of a given defect varies from strain to strain (1,2,5,6). For example, T helper cell hyperfunction plays a dominant role in the disease of MRL/1 mice (6-10), whereas primary B cell abnormalities have been identified in BXSB, NZB, and (NZB × NZW)F1 (NZB/W) mice (1,2,6,(11)(12)(13)(14). In fact, these latter mice, unlike MRL/1 mice (7,9), develop SLE despite neonatal thymectomy (1,2,7,15).…”

mentioning

confidence: 99%

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B cell dependence on and response to accessory signals in murine lupus strains.

Prud’homme¹,

Balderas²,

Dixon³

et al. 1983

The Journal of Experimental Medicine

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B cell hyperactivity, a feature common to all lupus-prone murine strains, may be caused by hyperresponsiveness to, overproduction of, or bypassing of certain signals required for B cell activation, proliferation, and differentiation. In this study, we have compared the responses of B cells from three lupus-prone strains of mice (BXSB males, MRL and NZB/W females) and normal strains in a number of assays for which two or more signals are required to obtain a response. In medium to low density cultures of B cells from BXSB and NZB/W but not MRL/l lupus mice, the cells' proliferation induced by bacterial lipopolysaccharide (LPS) or anti-mu antibody was much higher than that of B cells from normal controls. At low B cell density, polyclonal activation by these substances and subsequent Ig secretion were dependent on accessory signals present in supernatants of concanavalin A-treated normal lymphocytes (CAS) or on the MRL/l proliferating T cell-derived B cell differentiation factor (L-BCDF) in both lupus-prone and immunologically normal mice. However, the responses of B cells from BXSB and NZB/W, but not MRL/l, mice to these accessory signals were higher than those of normal mice. Ig synthesis by fresh B cells of BXSB and NZB/W mice cultured in the absence of mitogens but in the presence of CAS or L-BCDF was higher than by similar cells from other strains, suggesting an increased frequency of B cells activated in vivo in these two autoimmune strains of mice. The patterns of IgG subclass secretion in response to LPS (without added CAS or L-BCDF) were abnormal in all lupus strains, with a predominance of IgG2b and/or IgG2a and low levels of IgG3, contrary to normal B cells for which IgG3 synthesis predominated. However, IgG1 synthesis in vitro by autoimmune and normal B cells alike was highly dependent on T cell-derived soluble mediators. Antigen-specific responses to SRBC in vitro of B cells from all lupus strains, like those of B cells from normal strains, required a minimum of three signals (antigen, LPS, T cell-derived antigen nonspecific helper factors). Yet, once triggered, B cells of BXSB and NZB/W mice gave higher responses than those of the other strains. We conclude that B cells of lupus mice have signal requirements similar to those of normal mice. Nevertheless, B cells of BXSB and NZB/W, but not MRL/l, lupus mice hyperrespond or process some accessory signals abnormally.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 57%

Section: Lps-and Anti-#-mediated Proliferation In Low and Medium Densmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

B cell dependence on and response to accessory signals in murine lupus strains.

Prud’homme¹,

Balderas²,

Dixon³

et al. 1983

The Journal of Experimental Medicine

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show abstract

“…Deficiency of suppressor T cells has been described in children with Down's syndrome [5]. The study of murine systemic lupus ery thematosus (SLE), a disease associated with the presence of autoantibodics, has revealed a primary B cell abnormality [15][16][17], Re cently, monoclonal antibodies that define differentiation antigens on B lymphocyte subsets have been described [2,3,11,14], Because both aging and Down's syndrome are associated with autoimmune phenomena, it is likely that they might also have primary B cell abnormality similar to that seen in murine SLE. Therefore, in this investigation we have examined B lymphocyte subsets us ing FMC1 (that defines all B lymphocytes) and FMC7 (that defines a subset of B lym phocytes) monoclonal antibodies [2,3], and fluorescence-activated cell sorter (FACS IV), in aging humans and patients with Down's syndrome.…”

mentioning

confidence: 99%

Monoclonal Antibody-Defined B Cell Subsets in Aging Humans and Down’s Syndrome

Gupta

Zola²,

Brooks

et al. 1984

Gerontology

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Peripheral blood from aging and young humans and patients with Down’s syndrome, and from age- and sex-matched controls, was studied for the proportions of surface immunoglobulin (SIg⁺) bearing and monoclonal antibodies FMC1, and FMC7 defined B lymphocytes and B lymphocyte subsets using fluorescent-activated cell sorter. In aging humans, the proportion of SIg⁺ and FMC1⁺ (that detect all B lymphocytes) were comparable to simultaneously studied healthy young controls. However, FMC7⁺ (that detects a subset of B cells) B cells were significantly (p < 0.05) increased when compared to young subjects. In aging subjects, the proportions of FMC7⁺ B cells were comparable to their FMC1⁺ B cells, whereas in young subjects FMC7⁺ B cells were a subset of FMC1⁺ B cells. In Down’s syndrome, a phenomenon similar to aging humans was observed, that is the proportions of FMC7⁺ were increased when compared to age- and sex-matched controls and were comparable to their own FMC1⁺ B cells. This study demonstrates the abnormality of B lymphocytes in human aging and Down’s syndrome. The significance of these findings is discussed.