Gut microbes shape our antibodies before we are infected by pathogens


Date:
August 5, 2020
Source:
University of Bern
Summary:
Because the microbiota is so complex, containing hundreds of
different bacterial species, it is not known how the presence of
microbes in the intestine shaped the antibodies that are present
even before we are challenged by an infection. Researchers have
now shown how these beneficial microbes reprogram the repertoire
of white blood B cells that produce antibodies and how this helps
counter infections.



FULL STORY ==========================================================================
B cells are white blood cells that develop to produce antibodies. These antibodies, or immunoglobulins, can bind to harmful foreign particles
(such as viruses or disease-causing bacteria) to stop them invading and infecting the body's cells. Each B cell carries an individual B cell
receptor (BCR) which determines which particles it can bind, rather
like each lock accepts a different key. There are many millions of B
cells with different receptors in the body. This immense diversity comes
from rearranging the genes that code these receptors, so the receptor is slightly different in every B cell resulting in billions of possibilities
of different harmful molecules that could be recognized. Intestinal
microbes trigger expansion of these B cell populations and antibody
production, but until now it was unknown whether this was a random
process, or whether the molecules of the intestinal microbes themselves influence the outcome.


==========================================================================
In a research article published in the journal Nature, Dr. Hai Li,
Dr. Julien Limenitakis, Prof. Stephanie Ganal-Vonarburg and Prof. Andrew Macpherson of the Department for BioMedical Research, University of Bern,
and Inselspital, University Hospital Bern, have analyzed the billions
of genes that code the antibodies in a system that allows the responses
to individual benign intestinal microbes to be understood.

The range of available antibodies depends on where beneficial microbes
are in the body The number of benign microbes living in our intestines
is about the same as the number of cells in our body. Mostly these
bacteria stay within the intestinal tube rather than penetrate the body tissues. Unfortunately, some penetration is unavoidable, because the
intestine only has a single layer of cells that separate the inside of
the tube from blood vessels that we need to absorb our food.

Dr. Limenitakis used specially designed computer programs to process
millions of genetic sequences that compare the antibody repertoire
from B cells, depending on whether the microbes stay in the intestine,
or whether they reach the bloodstream. In both cases the antibody
repertoire is altered, but in rather different ways depending on how
the exposure occurs.

"Interestingly, this is rather predictable depending on the microbe
concerned and where it is in the body, indicating that the intestinal
microbes direct the development of our antibodies before we get a
serious infection and this process is certainly not random," explains Ganal-Vonarburg.

There are different sorts of antibodies in the lining of the intestine
(IgA) compared with the bloodstream (IgM and IgG). Using the powerful
genetic analysis, the researchers showed that the range of different
antibodies produced in the intestine was far less that those produced in central body tissues. This means that once microbes get into the body,
the immune system has many more possibilities to neutralize and eliminate
them, whereas antibodies in the intestine mainly just bind the bacterial molecules that they can see at any one time.

How the antibodies change when the body is exposed to different microbes
Over their life-span mammals face a huge variety of different microbial challenges. It was therefore important to know how once the antibody
repertoire could change once had been shaped by a particular microbe when something else came along. The research team answered this question by
testing what happened with the same microbe at different sites or with
two different microbes on after another.

Although intestinal microbes do not directly produce an especially wide
range of different antibodies, they sensitize the central immune tissues
to produce antibodies if the microbe gets into the bloodstream. When
a second microbes comes along, the rather limited intestinal antibody
response changes to accommodate this microbe (rather like changing the
lock in one's door). This is different from what happens when microbes
get into the blood stream to reach the central body tissues when a second
set of antibodies is made without compromising the first response to
the original microbes (like installing another lock, so the door can be
opened with different keys). This shows that central body tissues have
the capacity to remember a range of different microbial species and to
avoid the dangers of sepsis. It also shows that different B cell immune strategies in different body compartments are important for maintenance
of our peaceful existence with our microbial passengers.

Dr. Li comments that "Our data show for the first time that not only
the composition of our intestinal microbiota, but also the timing and
sequence of exposure to certain members of the commensal microbiota,
happening predominantly during the first waves of colonisations during
early life, have an outcome on the resulting B cell receptor repertoire
and subsequent immunity to pathogens."

========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Hai Li, Julien P. Limenitakis, Victor Greiff, Bahtiyar Yilmaz,
Olivier
Scha"ren, Camilla Urbaniak, Mirjam Zu"nd, Melissa A. E. Lawson,
Ian D.

Young, Sandra Rupp, Mathias Heikenwa"lder, Kathy D. McCoy,
Siegfried Hapfelmeier, Stephanie C. Ganal-Vonarburg, Andrew
J. Macpherson. Mucosal or systemic microbiota exposures shape the
B cell repertoire. Nature, 2020; DOI: 10.1038/s41586-020-2564-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200805124038.htm

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